UNC13D (unc-13 homolog D)

Gene

• Entrez ID: 201294
• Gene name: Unc-13 homolog D
• Gene symbol: UNC13D
• Synonyms: FHL3, HLH3, HPLH3, Munc13-4
• Chromosome: 17
• Chromosome location: 17q25.1
• Summary: This gene encodes a protein that is a member of the UNC13 family, containing similar domain structure as other family members but lacking an N-terminal phorbol ester-binding C1 domain present in other Munc13 proteins. The protein appears to play a role in

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs117221419	T>G	Conflicting-interpretations-of-pathogenicity, likely-benign, uncertain-significance	Coding sequence variant, missense variant
rs121434352	G>A,C	Pathogenic	Coding sequence variant, missense variant, stop gained
rs121434353	A>G	Pathogenic	Coding sequence variant, missense variant
rs121434354	A>C,T	Pathogenic	Coding sequence variant, missense variant
rs138760432	C>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs142335129	G>C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs144968313	T>G	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs149871493	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs201908137	C>A,T	Pathogenic	Splice donor variant
rs202020396	G>A,T	Likely-pathogenic	Stop gained, coding sequence variant, missense variant
rs747169857	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs754621494	T>C,G	Pathogenic	Coding sequence variant, missense variant
rs754882266	C>T	Likely-pathogenic	Splice donor variant
rs763117746	C>A,T	Pathogenic	Coding sequence variant, stop gained, missense variant
rs764196809	CCCT>-	Pathogenic	Coding sequence variant, frameshift variant
rs765034513	C>T	Likely-pathogenic	Intron variant
rs766657895	G>A	Pathogenic	Coding sequence variant, stop gained
rs777759523	C>T	Pathogenic	Splice donor variant
rs796065024	AGCGCGCTGCAC>-	Pathogenic	Coding sequence variant, inframe deletion
rs796065025	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs796065026	->A	Pathogenic	Coding sequence variant, frameshift variant
rs910650073	T>C	Pathogenic	Splice acceptor variant
rs933702160	C>G	Pathogenic	Splice donor variant
rs959968589	G>A	Pathogenic	Intron variant
rs1157287613	G>A	Pathogenic	Coding sequence variant, stop gained
rs1165696705	C>G,T	Likely-pathogenic	Splice donor variant
rs1274685768	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs1388957809	C>G	Likely-pathogenic	Splice acceptor variant
rs1555600214	C>T	Likely-pathogenic	Splice donor variant
rs1555601754	A>T	Pathogenic	Stop gained, coding sequence variant
rs1555601863	C>T	Likely-pathogenic	Splice acceptor variant
rs1567816070	->TCCA	Pathogenic	Frameshift variant, coding sequence variant
rs1567818219	ATCTCATGGC>TCGGACAAGGTA	Pathogenic	Frameshift variant, coding sequence variant
rs1567818774	G>A	Pathogenic	Stop gained, coding sequence variant
rs1599414759	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017327	hsa-miR-335-5p	Microarray	18185580
MIRT023568	hsa-miR-1-3p	Proteomics	18668040
MIRT032278	hsa-let-7b-5p	Proteomics	18668040
MIRT044594	hsa-miR-320a	CLASH	23622248
MIRT650869	hsa-miR-665	HITS-CLIP	23824327
MIRT650868	hsa-miR-6887-3p	HITS-CLIP	23824327
MIRT650867	hsa-miR-6795-3p	HITS-CLIP	23824327
MIRT650866	hsa-miR-6892-3p	HITS-CLIP	23824327
MIRT650865	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT650864	hsa-miR-4469	HITS-CLIP	23824327
MIRT650863	hsa-miR-7113-3p	HITS-CLIP	23824327
MIRT650862	hsa-miR-4287	HITS-CLIP	23824327
MIRT650861	hsa-miR-4685-3p	HITS-CLIP	23824327
MIRT650860	hsa-miR-1207-5p	HITS-CLIP	23824327
MIRT650859	hsa-miR-4763-3p	HITS-CLIP	23824327
MIRT650858	hsa-miR-4736	HITS-CLIP	23824327
MIRT650857	hsa-miR-6826-3p	HITS-CLIP	23824327
MIRT650856	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT650855	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT650854	hsa-miR-6867-3p	HITS-CLIP	23824327
MIRT650853	hsa-miR-7150	HITS-CLIP	23824327
MIRT650852	hsa-miR-3180-5p	HITS-CLIP	23824327
MIRT650869	hsa-miR-665	HITS-CLIP	23824327
MIRT650868	hsa-miR-6887-3p	HITS-CLIP	23824327
MIRT650867	hsa-miR-6795-3p	HITS-CLIP	23824327
MIRT650866	hsa-miR-6892-3p	HITS-CLIP	23824327
MIRT650865	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT650864	hsa-miR-4469	HITS-CLIP	23824327
MIRT650863	hsa-miR-7113-3p	HITS-CLIP	23824327
MIRT650862	hsa-miR-4287	HITS-CLIP	23824327
MIRT650861	hsa-miR-4685-3p	HITS-CLIP	23824327
MIRT650860	hsa-miR-1207-5p	HITS-CLIP	23824327
MIRT650859	hsa-miR-4763-3p	HITS-CLIP	23824327
MIRT650858	hsa-miR-4736	HITS-CLIP	23824327
MIRT650857	hsa-miR-6826-3p	HITS-CLIP	23824327
MIRT650856	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT650855	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT650854	hsa-miR-6867-3p	HITS-CLIP	23824327
MIRT650853	hsa-miR-7150	HITS-CLIP	23824327
MIRT650852	hsa-miR-3180-5p	HITS-CLIP	23824327
MIRT1475346	hsa-miR-1254	CLIP-seq
MIRT1475347	hsa-miR-1343	CLIP-seq
MIRT1475348	hsa-miR-1915	CLIP-seq
MIRT1475349	hsa-miR-3116	CLIP-seq
MIRT1475350	hsa-miR-3176	CLIP-seq
MIRT1475351	hsa-miR-361-3p	CLIP-seq
MIRT1475352	hsa-miR-3922-3p	CLIP-seq
MIRT1475353	hsa-miR-4436b-3p	CLIP-seq
MIRT1475354	hsa-miR-4645-5p	CLIP-seq
MIRT1475355	hsa-miR-4673	CLIP-seq
MIRT1475356	hsa-miR-4685-5p	CLIP-seq
MIRT1475357	hsa-miR-4701-5p	CLIP-seq
MIRT1475358	hsa-miR-516a-3p	CLIP-seq
MIRT1475359	hsa-miR-588	CLIP-seq
MIRT2143236	hsa-miR-1827	CLIP-seq
MIRT2143237	hsa-miR-1909	CLIP-seq
MIRT2143238	hsa-miR-3612	CLIP-seq
MIRT2143239	hsa-miR-3689a-3p	CLIP-seq
MIRT2143240	hsa-miR-3689c	CLIP-seq
MIRT2143241	hsa-miR-4728-5p	CLIP-seq
MIRT2143242	hsa-miR-650	CLIP-seq
MIRT2143243	hsa-miR-940	CLIP-seq
MIRT2363529	hsa-miR-129-3p	CLIP-seq
MIRT2363530	hsa-miR-3166	CLIP-seq
MIRT2363531	hsa-miR-4476	CLIP-seq
MIRT2363532	hsa-miR-4700-3p	CLIP-seq
MIRT2363533	hsa-miR-548g	CLIP-seq
MIRT2363534	hsa-miR-922	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002432	Process	Granuloma formation	IEA
GO:0002467	Process	Germinal center formation	IEA
GO:0005515	Function	Protein binding	IPI	15548590, 16278825, 25312756, 26627825
GO:0005576	Component	Extracellular region	TAS
GO:0005764	Component	Lysosome	IDA	15548590
GO:0005770	Component	Late endosome	IEA
GO:0005829	Component	Cytosol	IDA
GO:0006909	Process	Phagocytosis	IEA
GO:0016020	Component	Membrane	IEA
GO:0031267	Function	Small GTPase binding	IDA	22899725
GO:0031267	Function	Small GTPase binding	IPI	22899725
GO:0033093	Component	Weibel-Palade body	IDA	22899725
GO:0035578	Component	Azurophil granule lumen	TAS
GO:0043231	Component	Intracellular membrane-bounded organelle	IDA
GO:0043304	Process	Regulation of mast cell degranulation	IMP	15548590
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0043320	Process	Natural killer cell degranulation	IEA
GO:0045921	Process	Positive regulation of exocytosis	IMP	15548590, 19966785
GO:0046872	Function	Metal ion binding	IEA
GO:0051607	Process	Defense response to virus	IEA
GO:0055037	Component	Recycling endosome	IEA
GO:0070382	Component	Exocytic vesicle	IDA	17237785
GO:1900026	Process	Positive regulation of substrate adhesion-dependent cell spreading	IEA
GO:1903307	Process	Positive regulation of regulated secretory pathway	IGI	22899725

Other IDs

• MIM: 608897
• HGNC: 23147
• e!Ensembl: ENSG00000092929

Protein

• UniProt ID: Q70J99
• Protein name: Protein unc-13 homolog D (Munc13-4)
• Protein function: Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late endosomal structures, leading to the formation
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00168	C2	112 → 263	C2 domain	Domain
  PF10540	Membr_traf_MHD	830 → 894	Munc13 (mammalian uncoordinated) homology domain	Domain
  PF00168	C2	925 → 1039	C2 domain	Domain

• Sequence:

  MATLLSHPQQRPPFLRQAIKIRRRRVRDLQDPPPQMAPEIQPPSHHFSPEQRALLYEDAL
  YTVLHRLGHPEPNHVTEASELLRYLQEAFHVEPEEHQQTLQRVRELEKPIFCLKATVKQA
  KGILGKDVSGFSDPYCLLGIEQGVGVPGGSPGSRHRQKAVVRHTIPEEETHRTQVITQTL
  NPVWDETFILEFEDITNASFHLDMWDLDTVESVRQKLGELTDLHGLRRIFKEARKDKGQD
  DFLGNVVLRLQDLRCREDQWYPLEPRTETYPDRGQCHLQFQLIHKRRATSASRSQPSYTV
  HLHLLQQLVSHEVTQHEAGSTSWDGSLSPQAATVLFLHATQKDLSDFHQSMAQWLAYSRL
  YQSLEFPSSCLLHPITSIEYQWIQGRLKAEQQEELAASFSSLLTYGLSLIRRFRSVFPLS
  VSDSPARLQSLLRVLVQMCKMKAFGELCPNTAPLPQLVTEALQTGTTEWFHLKQQHHQPM
  VQGIPEAGKALLGLVQDVIGDLHQCQRTWDKIFHNTLKIHLFSMAFRELQWLVAKRVQDH
  TTVVGDVVSPEMGESLFQLYISLKELCQLRMSSSERDGVLALDNFHRWFQPAIPSWLQKT
  YNEALARVQRAVQMDELVPLGELTKHSTSAVDLSTCFAQISHTARQLDWPDPEEAFMITV
  KFVEDTCRLALVYCSLIKARARELSSGQKDQGQAANMLCVVVNDMEQLRLVIGKLPAQLA
  WEALEQRVGAVLEQGQLQNTLHAQLQSALAGLGHEIRTGVRTLAEQLEVGIAKHIQKLVG
  VRESVLPEDAILPLMKFLEVELCYMNTNLVQENFSSLLTLLWTHTLTVLVEAAASQRSSS
  LASNRLKIALQNLEICFHAEGCGLPPKALHTATFQALQRDLELQAASSRELIRKYFCSRI
  QQQAETTSEELGAVTVKASYRASEQKLRVELLSASSLLPLDSNGSSDPFVQLTLEPRHEF
  PELAARETQKHKKDLHPLFDETFEFLVPAEPCRKAGACLLLTVLDYDTLGADDLEGEAFL
  PLREVPGLSGSEEPGEVPQTRLPLTYPAPNGDPILQLLEGRKGDREAQVFVRLRRHRAKQ
  ASQHALRPAP

• Sequence length: 1090

Pathways

Reactome:

Neutrophil degranulation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505
Hemophagocytic lymphohistiocytosis	HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 3, Familial hemophagocytic lymphohistiocytosis	rs796065024, rs796065025, rs796065026, rs777759523, rs121434352, rs201908137, rs121434353, rs121434354, rs483352901, rs104893996, rs121918540, rs1599398298, rs121918541, rs1599395085, rs2146217813, rs104894176, rs104894180, rs28933973, rs104894181, rs104894182, rs104894183, rs28933376, rs771552960, rs786205093, rs193302876, rs61736587, rs431905512, rs794729649, rs751161742, rs751247865, rs766657895, rs140148806, rs747169857, rs1060499556, rs764196809, rs1555601863, rs1555600214, rs754621494, rs1555768979, rs578092914, rs147035858, rs189650890, rs752858869, rs147462227, rs1554867753, rs754882266, rs959968589, rs1555601754, rs1555769166, rs773360200, rs768849283, rs1564723653, rs763117746, rs1567818774, rs1567816070, rs1278701043, rs1567818219, rs1568463402, rs1564724291, rs1274685768, rs776571416, rs201032696, rs1157287613, rs141717050, rs1165696705, rs1388957809, rs765034513, rs1589233357, rs910650073, rs933702160, rs1584062332, rs200430442, rs776299562, rs1599414759, rs1848204643, rs1442964152, rs2064936948, rs1041960684, rs921624651, rs2064960126, rs143184345	25553300, 16278825, 14622600, 24139496, 19704116, 23180437, 21674762, 21931115, 24470399, 21248318, 15703195, 24825797, 21755595, 24842371, 21152410, 20823128, 26342526, 23669735, 19484379, 25573973, 24935083, 17993578, 18492689, 16825436
Hypofibrinogenemia	Hypofibrinogenemia	rs121913087, rs121913088, rs587776837, rs121909616, rs121909625, rs121909608, rs121909607, rs146387238, rs1578795296, rs1214070111, rs776817952, rs762964798, rs121909606, rs1414035000, rs1310452604
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	29610475

Unknown
Disease name	Disease term	dbSNP ID	References
Agranulocytosis	Agranulocytosis
Cardiovascular diseases	Cardiovascular Diseases		30595370
Fibrinogen deficiency	Fibrinogen Deficiency
Histiocytosis haematophagic	Histiocytosis haematophagic
Mental depression	Major Depressive Disorder	rs587778876, rs587778877	27777418
Prostatic neoplasms	Prostatic Neoplasms		29610475