NPHP4 (nephrocystin 4)

Gene

• Entrez ID: 261734
• Gene name: Nephrocystin 4
• Gene symbol: NPHP4
• Synonyms (NCBI Gene): POC10, SLSN4
• Chromosome: 1
• Chromosome location: 1p36.31
• Summary: This gene encodes a protein involved in renal tubular development and function. This protein interacts with nephrocystin, and belongs to a multifunctional complex that is localized to actin- and microtubule-based structures. Mutations in this gene are ass

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs17472401	G>A	Benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, non coding transcript variant
rs28940891	A>G	Pathogenic	Genic downstream transcript variant, coding sequence variant, non coding transcript variant, downstream transcript variant, missense variant
rs35575973	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, non coding transcript variant, intron variant, downstream transcript variant, synonymous variant, genic downstream transcript variant
rs35959882	T>C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, non coding transcript variant
rs112206586	T>A,G	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, missense variant, coding sequence variant
rs115272639	C>T	Conflicting-interpretations-of-pathogenicity	5 prime UTR variant, non coding transcript variant, synonymous variant, coding sequence variant
rs116606479	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Genic downstream transcript variant, downstream transcript variant, missense variant, coding sequence variant, non coding transcript variant
rs117898549	T>C	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	5 prime UTR variant, non coding transcript variant, missense variant, coding sequence variant
rs137852918	C>A	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs137852919	G>A	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs137852920	G>A,T	Likely-pathogenic, pathogenic	Stop gained, non coding transcript variant, synonymous variant, coding sequence variant
rs137852922	G>A	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs137852923	G>A	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs139767853	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance, benign	Genic downstream transcript variant, non coding transcript variant, missense variant, coding sequence variant
rs146948888	C>T	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, synonymous variant, coding sequence variant, genic downstream transcript variant, downstream transcript variant
rs183885357	C>T	Conflicting-interpretations-of-pathogenicity, benign	Downstream transcript variant, non coding transcript variant, missense variant, coding sequence variant, genic downstream transcript variant
rs191913664	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, intron variant, coding sequence variant, non coding transcript variant
rs199557439	C>T	Conflicting-interpretations-of-pathogenicity	Intron variant, coding sequence variant, synonymous variant, non coding transcript variant
rs199628481	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Intron variant, coding sequence variant, synonymous variant, non coding transcript variant
rs199925943	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, non coding transcript variant, intron variant, synonymous variant, genic downstream transcript variant
rs200104274	T>C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, non coding transcript variant
rs200166175	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, non coding transcript variant, missense variant, genic downstream transcript variant, downstream transcript variant
rs200952409	G>T	Conflicting-interpretations-of-pathogenicity	Intron variant
rs201065230	A>G	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Intron variant, genic upstream transcript variant, non coding transcript variant, missense variant, coding sequence variant, 5 prime UTR variant
rs201069164	G>A	Conflicting-interpretations-of-pathogenicity	Upstream transcript variant, synonymous variant, intron variant, non coding transcript variant, genic upstream transcript variant, coding sequence variant, 5 prime UTR variant
rs201074950	G>A,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, downstream transcript variant, missense variant, coding sequence variant, genic downstream transcript variant
rs201090359	G>A,C	Conflicting-interpretations-of-pathogenicity	Synonymous variant, non coding transcript variant, intron variant, missense variant, coding sequence variant
rs201192584	G>A	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, coding sequence variant, synonymous variant
rs201488441	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, 5 prime UTR variant, synonymous variant, non coding transcript variant
rs201903713	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, coding sequence variant, synonymous variant
rs368961102	C>T	Conflicting-interpretations-of-pathogenicity	Intron variant, genic upstream transcript variant
rs370210428	G>A	Pathogenic	Intron variant, genic upstream transcript variant, non coding transcript variant, coding sequence variant, 5 prime UTR variant, stop gained
rs370899989	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Intron variant
rs372430727	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Non coding transcript variant, coding sequence variant, synonymous variant
rs373182062	G>A,C	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant, non coding transcript variant
rs373369949	G>A,T	Likely-pathogenic	Non coding transcript variant, genic downstream transcript variant, coding sequence variant, missense variant, intron variant
rs374003717	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Synonymous variant, coding sequence variant, genic downstream transcript variant, non coding transcript variant
rs374141736	C>G,T	Pathogenic	Splice donor variant
rs374354239	G>A	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, synonymous variant, genic downstream transcript variant, coding sequence variant, intron variant
rs374690894	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant, missense variant, non coding transcript variant
rs375493384	C>G,T	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, synonymous variant, genic downstream transcript variant, coding sequence variant, downstream transcript variant
rs398124289	->GAGCG	Pathogenic	Frameshift variant, non coding transcript variant, genic downstream transcript variant, coding sequence variant, downstream transcript variant
rs528547815	G>A,T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant, genic downstream transcript variant, non coding transcript variant
rs545943420	G>A	Conflicting-interpretations-of-pathogenicity	Non coding transcript variant, genic upstream transcript variant, coding sequence variant, synonymous variant, 5 prime UTR variant
rs547495754	G>A	Uncertain-significance, pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs569364202	G>A	Pathogenic	Non coding transcript variant, downstream transcript variant, genic downstream transcript variant, missense variant, coding sequence variant
rs570380438	A>T	Conflicting-interpretations-of-pathogenicity	Intron variant
rs747699128	GAGG>-	Likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant
rs754862360	G>-,GG	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant, intron variant, 5 prime UTR variant
rs756449736	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, intron variant, coding sequence variant, non coding transcript variant
rs758275952	G>A	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs758757125	G>A	Conflicting-interpretations-of-pathogenicity	Downstream transcript variant, synonymous variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant
rs762371581	TAGA>-	Pathogenic	Genic downstream transcript variant, non coding transcript variant, frameshift variant, coding sequence variant
rs762709199	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant, non coding transcript variant, genic downstream transcript variant, downstream transcript variant
rs775612958	G>A	Likely-pathogenic	Coding sequence variant, intron variant, non coding transcript variant, genic downstream transcript variant, stop gained
rs1025515771	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1210874691	C>A	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained, 5 prime UTR variant
rs1278089386	A>-	Pathogenic	Genic downstream transcript variant, coding sequence variant, frameshift variant, non coding transcript variant
rs1368105372	TGAG>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1487910110	C>T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1553178047	GTT>CCACG	Likely-pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant
rs1553200990	TCAA>-	Pathogenic	Intron variant, 5 prime UTR variant, upstream transcript variant, non coding transcript variant, genic upstream transcript variant, frameshift variant, coding sequence variant
rs1557588167	G>-	Pathogenic	Coding sequence variant, genic downstream transcript variant, frameshift variant, non coding transcript variant
rs1557768696	->GG	Likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant, 5 prime UTR variant
rs1570504754	->GG	Likely-pathogenic	Frameshift variant, non coding transcript variant, 5 prime UTR variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1190809	hsa-miR-15a	CLIP-seq
MIRT1190810	hsa-miR-15b	CLIP-seq
MIRT1190811	hsa-miR-16	CLIP-seq
MIRT1190812	hsa-miR-195	CLIP-seq
MIRT1190813	hsa-miR-214	CLIP-seq
MIRT1190814	hsa-miR-320e	CLIP-seq
MIRT1190815	hsa-miR-3619-5p	CLIP-seq
MIRT1190816	hsa-miR-370	CLIP-seq
MIRT1190817	hsa-miR-424	CLIP-seq
MIRT1190818	hsa-miR-4291	CLIP-seq
MIRT1190819	hsa-miR-4455	CLIP-seq
MIRT1190820	hsa-miR-4650-5p	CLIP-seq
MIRT1190821	hsa-miR-4731-5p	CLIP-seq
MIRT1190822	hsa-miR-497	CLIP-seq
MIRT1190823	hsa-miR-609	CLIP-seq
MIRT1190824	hsa-miR-646	CLIP-seq
MIRT1190825	hsa-miR-761	CLIP-seq
MIRT1190826	hsa-miR-922	CLIP-seq
MIRT2055230	hsa-miR-1205	CLIP-seq
MIRT2055231	hsa-miR-1909	CLIP-seq
MIRT2055232	hsa-miR-4436b-3p	CLIP-seq
MIRT2055233	hsa-miR-4459	CLIP-seq
MIRT2055234	hsa-miR-4722-5p	CLIP-seq
MIRT2055235	hsa-miR-4779	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005198	Function	Structural molecule activity	NAS	12006559
GO:0005515	Function	Protein binding	IPI	12244321, 15661758, 16339905, 17558407, 20664800, 21224891, 21357692, 21565611, 22654112, 22863007, 26638075, 26644512, 27173435, 29959317, 33961781
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IEA
GO:0005813	Component	Centrosome	IDA	21399614
GO:0005813	Component	Centrosome	IEA
GO:0005814	Component	Centriole	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IEA
GO:0005911	Component	Cell-cell junction	IDA	21565611
GO:0005923	Component	Bicellular tight junction	IEA
GO:0005929	Component	Cilium	IEA
GO:0007165	Process	Signal transduction	NAS	12244321
GO:0007632	Process	Visual behavior	NAS	12205563
GO:0016604	Component	Nuclear body	IDA
GO:0030036	Process	Actin cytoskeleton organization	NAS	12006559
GO:0030317	Process	Flagellated sperm motility	IEA
GO:0032391	Component	Photoreceptor connecting cilium	IEA
GO:0035845	Process	Photoreceptor cell outer segment organization	IEA
GO:0035869	Component	Ciliary transition zone	IBA
GO:0035869	Component	Ciliary transition zone	IEA
GO:0036064	Component	Ciliary basal body	IBA
GO:0036064	Component	Ciliary basal body	IEA
GO:0042995	Component	Cell projection	IEA
GO:0045494	Process	Photoreceptor cell maintenance	IEA
GO:0060041	Process	Retina development in camera-type eye	IEA
GO:0070161	Component	Anchoring junction	IEA
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IBA
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IDA	22654112
GO:0090090	Process	Negative regulation of canonical Wnt signaling pathway	IEA
GO:0097470	Component	Ribbon synapse	IEA
GO:0097546	Component	Ciliary base	IBA
GO:0097546	Component	Ciliary base	IEA
GO:0097730	Component	Non-motile cilium	IBA
GO:0097730	Component	Non-motile cilium	IEA
GO:0098609	Process	Cell-cell adhesion	NAS	12006559
GO:0120206	Component	Photoreceptor distal connecting cilium	IEA
GO:1903348	Process	Positive regulation of bicellular tight junction assembly	IMP	19755384
GO:1904491	Process	Protein localization to ciliary transition zone	IBA

Other IDs

• MIM: 607215
• HGNC: 19104
• e!Ensembl: ENSG00000131697

Protein

• UniProt ID: O75161
• Protein name: Nephrocystin-4 (Nephroretinin)
• Protein function: Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module (PubMed:19755384, PubMed:21565611). Does not seem to be strictly required for ciliogenesis (PubMed:21565611). Required for building functi
• Tissue specificity: TISSUE SPECIFICITY: Expressed in kidney, skeletal muscle, heart and liver, and to a lesser extent in brain and lung. {ECO:0000269|PubMed:12244321}.
• Sequence:

  MNDWHRIFTQNVLVPPHPQRARQPWKESTAFQCVLKWLDGPVIRQGVLEVLSEVECHLRV
  SFFDVTYRHFFGRTWKTTVKPTKRPPSRIVFNEPLYFHTSLNHPHIVAVVEVVAEGKKRD
  GSLQTLSCGFGILRIFSNQPDSPISASQDKRLRLYHGTPRALLHPLLQDPAEQNRHMTLI
  ENCSLQYTLKPHPALEPAFHLLPENLLVSGLQQIPGLLPAHGESGDALRKPRLQKPITGH
  LDDLFFTLYPSLEKFEEELLELHVQDHFQEGCGPLDGGALEILERRLRVGVHNGLGFVQR
  PQVVVLVPEMDVALTRSASFSRKVVSSSKTSSGSQALVLRSRLRLPEMVGHPAFAVIFQL
  EYVFSSPAGVDGNAASVTSLSNLACMHMVRWAVWNPLLEADSGRVTLPLQGGIQPNPSHC
  LVYKVPSASMSSEEVKQVESGTLRFQFSLGSEEHLDAPTEPVSGPKVERRPSRKPPTSPS
  SPPAPVPRVLAAPQNSPVGPGLSISQLAASPRSPTQHCLARPTSQLPHGSQASPAQAQEF
  PLEAGISHLEADLSQTSLVLETSIAEQLQELPFTPLHAPIVVGTQTRSSAGQPSRASMVL
  LQSSGFPEILDANKQPAEAVSATEPVTFNPQKEESDCLQSNEMVLQFLAFSRVAQDCRGT
  SWPKTVYFTFQFYRFPPATTPRLQLVQLDEAGQPSSGALTHILVPVSRDGTFDAGSPGFQ
  LRYMVGPGFLKPGERRCFARYLAVQTLQIDVWDGDSLLLIGSAAVQMKHLLRQGRPAVQA
  SHELEVVATEYEQDNMVVSGDMLGFGRVKPIGVHSVVKGRLHLTLANVGHPCEQKVRGCS
  TLPPSRSRVISNDGASRFSGGSLLTTGSSRRKHVVQAQKLADVDSELAAMLLTHARQGKG
  PQDVSRESDATRRRKLERMRSVRLQEAGGDLGRRGTSVLAQQSVRTQHLRDLQVIAAYRE
  RTKAESIASLLSLAITTEHTLHATLGVAEFFEFVLKNPHNTQHTVTVEIDNPELSVIVDS
  QEWRDFKGAAGLHTPVEEDMFHLRGSLAPQLYLRPHETAHVPFKFQSFSAGQLAMVQASP
  GLSNEKGMDAVSPWKSSAVPTKHAKVLFRASGGKPIAVLCLTVELQPHVVDQVFRFYHPE
  LSFLKKAIRLPPWHTFPGAPVGMLGEDPPVHVRCSDPNVICETQNVGPGEPRDIFLKVAS
  GPSPEIKDFFVIIYSDRWLATPTQTWQVYLHSLQRVDVSCVAGQLTRLSLVLRGTQTVRK
  VRAFTSHPQELKTDPKGVFVLPPRGVQDLHVGVRPLRAGSRFVHLNLVDVDCHQLVASWL
  VCLCCRQPLISKAFEIMLAAGEGKGVNKRITYTNPYPSRRTFHLHSDHPELLRFREDSFQ
  VGGGETYTIGLQFAPSQRVGEEEILIYINDHEDKNEEAFCVKVIYQ

• Sequence length: 1426

Pathways

Reactome:

Signaling by Hippo
Anchoring of the basal body to the plasma membrane

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Cerebello-oculo-renal syndrome (nephronophthisis, oculomotor apraxia and cerebellar abnormalities)	Pathogenic	rs137852920	RCV000162133	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Likely pathogenic	rs761142233	RCV005922472	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Clear cell carcinoma of kidney	Likely pathogenic	rs761142233	RCV005922471	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Infertility disorder	Pathogenic	rs137852920	RCV000162133	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Kidney disorder	Likely pathogenic; Pathogenic	rs756111113, rs780905861	RCV002294437 RCV002294447	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Lung cancer	Pathogenic	rs1419875412	RCV005909212	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Melanoma	Pathogenic	rs1419875412	RCV005909211	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Nephronophthisis	Likely pathogenic; Pathogenic	rs564232197, rs2102455183, rs1557616007, rs1168286961, rs770306587, rs2101924403, rs770357627, rs756111113, rs761142233, rs753774833, rs776535691, rs1474013513, rs763668545, rs1642345798, rs2100405990, rs2100466824, rs2100733826, rs2101131514, rs2100733763, rs746243637, rs1557895715, rs780268322, rs2100678099, rs1235304713, rs1195128294, rs775221217, rs137852918, rs137852919, rs137852920, rs1278089386, rs137852922, rs137852923, rs1414888414, rs1384212298, rs777884325, rs1557880019, rs1257152837, rs2523666112, rs768093553, rs2523983926, rs1642683882, rs771318550, rs2523226313, rs867255315, rs2100620614, rs2523692876, rs765460065, rs1294693530, rs2521518413, rs2523978952, rs2521519226, rs1439234327, rs2521715879, rs1179512510, rs778642094, rs1644831295, rs398124289, rs1025515771, rs1553200990, rs1553178047, rs370210428, rs1557580413, rs1368105372, rs374141736, rs1210874691, rs758275952, rs775612958, rs754862360, rs1652115764, rs1647148516, rs780905861, rs1237376396, rs113413307, rs781558715, rs757412845, rs751662952, rs997408852, rs748950922, rs1643882944, rs1644833186, rs1430741326	RCV001379646 RCV001378643 RCV001380253 RCV001385363 RCV001386662 RCV001381856 RCV001380666 RCV001882599 RCV002034603 RCV001941650 RCV001908235 RCV001886932 RCV001888238 RCV001964323 RCV001927487 RCV001897546 RCV001942179 RCV001920754 RCV002031695 RCV002001257 RCV001966628 RCV001940801 RCV001975084 RCV001944218 RCV002023725 RCV003586322 RCV005089152 RCV000705098 RCV001851618 RCV002512712 RCV000234814 RCV000234826 RCV003075440 RCV002634334 RCV002630045 RCV002589982 RCV002810873 RCV002806437 RCV002871998 RCV002862764 RCV002852909 RCV003032098 RCV003039616 RCV003586677 RCV003587012 RCV003586880 RCV003587225 RCV003587375 RCV003587509 RCV003587636 RCV003749261 RCV003749450 RCV003749831 RCV003749587 RCV003749579 RCV003748016 RCV003748672 RCV003857628 RCV003879372 RCV000812054 RCV001381479 RCV003117367 RCV002532689 RCV001237139 RCV001380731 RCV001244264 RCV001379686 RCV000796841 RCV000792272 RCV001328313 RCV003586262 RCV001052330 RCV005093421 RCV001195281 RCV003117841 RCV001223028 RCV001209115 RCV001213129 RCV001221547 RCV001229763 RCV001243421 RCV001230177 RCV001328315 RCV001328318 RCV001328314 RCV001328316	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Nephronophthisis 4	Likely pathogenic; Pathogenic	rs1557616007, rs1168286961, rs770306587, rs756111113, rs1204924769, rs761142233, rs776535691, rs1474013513, rs2100466824, rs1235304713, rs137852918, rs137852919, rs137852920, rs28940891, rs1278089386, rs137852923, rs1414888414, rs747699128, rs761183927, rs2522512934, rs2522589875, rs2523123174, rs2100620614, rs1179512510, rs1648391557, rs1025515771, rs1553200990, rs1553178047, rs1557768696, rs370210428, rs1368105372, rs374141736, rs1210874691, rs762371581, rs758275952, rs775612958, rs1570504754, rs754862360, rs780905861, rs1237376396, rs781558715, rs757412845, rs751662952, rs997408852, rs765043646, rs1271993311, rs1650418400, rs1419875412	RCV002493920 RCV002499802 RCV002488207 RCV001536003 RCV001535885 RCV005038321 RCV002482690 RCV005023376 RCV003448426 RCV002507624 RCV000003568 RCV000003569 RCV000003570 RCV000003571 RCV000003572 RCV000735764 RCV005019652 RCV000490323 RCV003236650 RCV003324646 RCV004577592 RCV004577593 RCV005030089 RCV005030206 RCV003991280 RCV002497256 RCV001193268 RCV002498877 RCV005414329 RCV005027837 RCV002493130 RCV005027909 RCV002485904 RCV002499381 RCV001730711 RCV001029764 RCV001029763 RCV001029787 RCV005021434 RCV004596424 RCV005401806 RCV002471048 RCV002283531 RCV002491732 RCV001257427 RCV005860197 RCV001281250 RCV001281249 RCV001281252 RCV001281251	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NPHP4-related disorder	Pathogenic; Likely pathogenic	rs1278089386, rs2523146231, rs2523690043, rs1025515771, rs370210428	RCV004532278 RCV004528619 RCV004537030 RCV004530676 RCV004733000	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Retinal dystrophy	Likely pathogenic; Pathogenic	rs370210428, rs1643875847, rs756111113	RCV004817922 RCV001075700 RCV001075741	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis pigmentosa	Likely pathogenic	rs752910449, rs2102003035	RCV001724796 RCV001724797	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Senior-Loken syndrome 4	Likely pathogenic; Pathogenic	rs1641316046, rs1557616007, rs1168286961, rs770306587, rs756111113, rs1204924769, rs761142233, rs776535691, rs1474013513, rs1235304713, rs775221217, rs1278089386, rs137852922, rs137852923, rs1414888414, rs747699128, rs2100620614, rs1179512510, rs1025515771, rs1553178047, rs370210428, rs1368105372, rs374141736, rs1210874691, rs762371581, rs758275952, rs780905861, rs781558715, rs751662952	RCV001331947 RCV002493920 RCV002499802 RCV002488207 RCV001536003 RCV001535885 RCV005038321 RCV002482690 RCV005023376 RCV002507624 RCV004785549 RCV002490303 RCV000003573 RCV000003574 RCV005019652 RCV000490323 RCV005030089 RCV005030206 RCV002497256 RCV002498877 RCV005027837 RCV002493130 RCV005027909 RCV002485904 RCV002499381 RCV002487641 RCV005021434 RCV001197495 RCV002504254 RCV002491732	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atypical hemolytic-uremic syndrome	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bardet-Biedl syndrome	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
BEHCET'S SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CAKUT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholestasis	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CHRONIC KIDNEY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ciliopathy	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital anomaly of kidney and urinary tract	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
focal and segmental glomerulosclerosis	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Focal segmental glomerulosclerosis	Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
JOUBERT SYNDROME 4	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
JUVENILE IDIOPATHIC ARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
JUVENILE NEPHRONOPHTHISIS	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leber congenital amaurosis	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lynch syndrome 1	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEPHRONOPHTHISIS 1	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEPHRONOPHTHISIS, FAMILIAL JUVENILE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Optic atrophy	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Ovarian cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Renal dysplasia and retinal aplasia	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINITIS PIGMENTOSA 1	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENIOR-LOKEN SYNDROME	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENIOR-LOKEN SYNDROME 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Conflicting classifications of pathogenicity; Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Arima syndrome	Arima Syndrome	BEFREE	17558409, 23574405		★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic kidney disease stage 5	Kidney Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathies	BEFREE	17558409		★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathy	Pubtator	21068128, 21357692	Associate	★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathies	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	22550138		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Conotruncal cardiac defects	Conotruncal cardiac defect	Pubtator	36789878	Associate	★☆☆☆☆ Found in Text Mining only
Disorder of eye	Disorder Of Eye	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial aplasia of the vermis	Cerebellar vermis agenesis	BEFREE	17558409, 23574405		★☆☆☆☆ Found in Text Mining only
Focal glomerulosclerosis	Glomerulosclerosis	BEFREE	17954299		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glomerulosclerosis Focal Segmental	Focal segmental glomerulosclerosis	Pubtator	34435324	Associate	★☆☆☆☆ Found in Text Mining only
Hepatic Fibrosis, Congenital	Congenital Hepatic Fibrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hydrocephalus, Normal Pressure	Hydrocephalus	BEFREE	14750102, 15776426		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Infertility Male	Male infertility	Pubtator	37831349	Associate	★☆☆☆☆ Found in Text Mining only
Juvenile nephronophthisis	Nephronophthisis	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kidney Diseases	Kidney Disease	BEFREE	17558409, 21555462		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kidney Diseases	Kidney disease	Pubtator	40725491	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kidney Failure Chronic	Kidney failure	Pubtator	25818963	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Neoplasms	Kidney neoplasm	Pubtator	24516231	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	22797725	Associate	★☆☆☆☆ Found in Text Mining only
Nephronophthisis	Nephronophthisis	BEFREE	11920287, 12205563, 12244321, 12872122, 15776426, 16339905, 17558409, 17954299, 31810733		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Nephronophthisis	Nephronophthisis	CLINVAR_DG	12205563, 12244321, 15776426		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Nephronophthisis	Nephronophthisis	GENOMICS_ENGLAND_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Nephronophthisis	Nephronophthisis	HPO_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEPHRONOPHTHISIS 2	Nephronophthisis	BEFREE	12872123		★☆☆☆☆ Found in Text Mining only
NEPHRONOPHTHISIS 3	Nephronophthisis	BEFREE	16724659		★☆☆☆☆ Found in Text Mining only
NEPHRONOPHTHISIS 4	Nephronophthisis	UNIPROT_DG	12205563, 12244321, 15776426, 16339905, 17558407, 22550138		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEPHRONOPHTHISIS 4	Nephronophthisis	GENOMICS_ENGLAND_DG	12205563, 12244321, 26346198		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEPHRONOPHTHISIS 4	Nephronophthisis	CLINVAR_DG	12205563		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Nephronophthisis 4	Nephronophthisis	Pubtator	12205563	Associate	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEPHRONOPHTHISIS 4	Nephronophthisis	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Nephronophthisis familial juvenile	Nephronophthisis	Pubtator	11920287, 12205563, 15776426, 17617513, 18076122, 21357692, 25818963, 31810733	Associate	★☆☆☆☆ Found in Text Mining only
Nephronophthisis type 4	Nephronophthisis	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Nephronophthisis, familial juvenile	Nephronophthisis	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Premature Menopause	Premature Menopause	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal corticomedullary cysts	Renal corticomedullary cysts	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal dysplasia and retinal aplasia (disorder)	Renal dysplasia and retinal aplasia	BEFREE	11920287, 16339905, 17558407		★☆☆☆☆ Found in Text Mining only
Renal dysplasia and retinal aplasia (disorder)	Renal dysplasia and retinal aplasia	ORPHANET_DG	22819833		★☆☆☆☆ Found in Text Mining only
Renal dysplasia and retinal aplasia (disorder)	Renal dysplasia and retinal aplasia	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Retinal Dystrophies	Retinal Dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	BEFREE	11920287, 12205563, 16339905		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis pigmentosa	Pubtator	11920287, 12205563	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Retinitis Pigmentosa	Retinitis Pigmentosa	LHGDN	16339905		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Rod-Cone Dystrophy	Rod-cone dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rotary Nystagmus	Rotary nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Senior Loken Syndrome	Senior-loken syndrome	Pubtator	11920287, 40725491	Associate	★☆☆☆☆ Found in Text Mining only
Senior-Loken syndrome	Senior-Loken Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENIOR-LOKEN SYNDROME 4	Senior-Loken Syndrome	CLINVAR_DG	12205563		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SENIOR-LOKEN SYNDROME 4	Senior-Loken Syndrome	GENOMICS_ENGLAND_DG	12205563		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SENIOR-LOKEN SYNDROME 4	Senior-Loken Syndrome	UNIPROT_DG	12244321, 15776426, 21546380, 22550138		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SENIOR-LOKEN SYNDROME 4	Senior-Loken Syndrome	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Situs ambiguus	Situs ambiguus	BEFREE	22550138		★☆☆☆☆ Found in Text Mining only