Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Gene ontology Other IDs Protein Associated diseases
Entrez ID	131377
Gene name	Kelch like family member 40
Gene symbol	KLHL40
Synonyms (NCBI Gene)	KBTBD5NEM8SRYPSYRP
Chromosome	3
Chromosome location	3p22.1
Summary	This gene encodes a protein containing a BACK domain, a BTB/POZ domain, and 5 Kelch repeats, however, its exact function is not known. The gene and the multi-domain protein structure are conserved across different taxa, including primates, rodents, chicke

Show/Hide all (17)

SNP ID	Visualize variation	Clinical significance	Consequence
rs139588377	C>A,T	Pathogenic, likely-benign	Stop gained, synonymous variant, coding sequence variant
rs367579275	G>A,T	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs397509419	G>A	Pathogenic	Missense variant, coding sequence variant
rs397509420	G>A,T	Pathogenic	Missense variant, coding sequence variant, stop gained
rs397509421	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs752493018	A>T	Likely-pathogenic	Splice acceptor variant
rs752734208	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs758188096	C>T	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs763283033	C>A,T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs777496833	T>A	Likely-pathogenic	Coding sequence variant, missense variant
rs778303947	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs778565563	G>C,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs1085307627	->G	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1186218257	G>T	Likely-pathogenic	Splice donor variant
rs1575218072	G>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1575218831	->A	Pathogenic	Frameshift variant, coding sequence variant
rs1575219191	T>A	Likely-pathogenic	Splice donor variant

Show/Hide all (44)

miRTarBase ID	miRNA	Experiments	Reference
MIRT648788	hsa-miR-15a-5p	HITS-CLIP	23824327
MIRT648787	hsa-miR-15b-5p	HITS-CLIP	23824327
MIRT648786	hsa-miR-16-5p	HITS-CLIP	23824327
MIRT648785	hsa-miR-195-5p	HITS-CLIP	23824327
MIRT648784	hsa-miR-424-5p	HITS-CLIP	23824327
MIRT648783	hsa-miR-497-5p	HITS-CLIP	23824327
MIRT648781	hsa-miR-6838-5p	HITS-CLIP	23824327
MIRT648782	hsa-miR-383-3p	HITS-CLIP	23824327
MIRT648780	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT648779	hsa-miR-212-5p	HITS-CLIP	23824327
MIRT648777	hsa-miR-3189-3p	HITS-CLIP	23824327
MIRT648778	hsa-miR-3124-3p	HITS-CLIP	23824327
MIRT648776	hsa-miR-6792-5p	HITS-CLIP	23824327
MIRT648775	hsa-miR-623	HITS-CLIP	23824327
MIRT648774	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT648773	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT648772	hsa-miR-502-5p	HITS-CLIP	23824327
MIRT648771	hsa-miR-647	HITS-CLIP	23824327
MIRT648770	hsa-miR-6842-3p	HITS-CLIP	23824327
MIRT648769	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT648768	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT648767	hsa-miR-521	HITS-CLIP	23824327
MIRT648788	hsa-miR-15a-5p	HITS-CLIP	23824327
MIRT648787	hsa-miR-15b-5p	HITS-CLIP	23824327
MIRT648786	hsa-miR-16-5p	HITS-CLIP	23824327
MIRT648785	hsa-miR-195-5p	HITS-CLIP	23824327
MIRT648784	hsa-miR-424-5p	HITS-CLIP	23824327
MIRT648783	hsa-miR-497-5p	HITS-CLIP	23824327
MIRT648781	hsa-miR-6838-5p	HITS-CLIP	23824327
MIRT648782	hsa-miR-383-3p	HITS-CLIP	23824327
MIRT648780	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT648779	hsa-miR-212-5p	HITS-CLIP	23824327
MIRT648777	hsa-miR-3189-3p	HITS-CLIP	23824327
MIRT648778	hsa-miR-3124-3p	HITS-CLIP	23824327
MIRT648776	hsa-miR-6792-5p	HITS-CLIP	23824327
MIRT648775	hsa-miR-623	HITS-CLIP	23824327
MIRT648774	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT648773	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT648772	hsa-miR-502-5p	HITS-CLIP	23824327
MIRT648771	hsa-miR-647	HITS-CLIP	23824327
MIRT648770	hsa-miR-6842-3p	HITS-CLIP	23824327
MIRT648769	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT648768	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT648767	hsa-miR-521	HITS-CLIP	23824327

Show/Hide all (21)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	28514442, 32296183
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	ISS
GO:0031397	Process	Negative regulation of protein ubiquitination	IBA
GO:0031398	Process	Positive regulation of protein ubiquitination	ISS
GO:0031463	Component	Cul3-RING ubiquitin ligase complex	IBA
GO:0031463	Component	Cul3-RING ubiquitin ligase complex	IEA
GO:0031463	Component	Cul3-RING ubiquitin ligase complex	ISS
GO:0031672	Component	A band	IBA
GO:0031672	Component	A band	IEA
GO:0031674	Component	I band	IBA
GO:0031674	Component	I band	IEA
GO:0032435	Process	Negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IBA
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	ISS
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IBA
GO:0048741	Process	Skeletal muscle fiber development	IBA
GO:0048741	Process	Skeletal muscle fiber development	IEA
GO:0048741	Process	Skeletal muscle fiber development	ISS
GO:0098528	Process	Skeletal muscle fiber differentiation	ISS
GO:1990756	Function	Ubiquitin-like ligase-substrate adaptor activity	IBA

MIM	HGNC	e!Ensembl
615340	30372	ENSG00000157119

Q2TBA0

Protein name

Kelch-like protein 40 (Kelch repeat and BTB domain-containing protein 5) (Sarcosynapsin)

Protein function

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development (PubMed:23746549). The BCR(KLHL40) complex acts by mediating ubiquitination and degradation of TFDP1, the

PDB

4ASC

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF00651	BTB	23 → 128	BTB/POZ domain	Domain
PF07707	BACK	133 → 239	BTB And C-terminal Kelch	Domain
PF01344	Kelch_1	452 → 497	Kelch motif	Repeat
PF01344	Kelch_1	499 → 540	Kelch motif	Repeat
PF01344	Kelch_1	546 → 596	Kelch motif	Repeat

Tissue specificity

TISSUE SPECIFICITY: Highly expressed in fetal (19, 23 and 31 weeks of gestation) and adult skeletal muscle; expression levels tend to be higher in fetal compared to postnatal muscles (at protein level). Also expressed in fetal and adult heart. {ECO:000026

Sequence

MALGLEQAEEQRLYQQTLLQDGLKDMLDHGKFLDCVVRAGEREFPCHRLVLAACSPYFRA
RFLAEPERAGELHLEEVSPDVVAQVLHYLYTSEIALDEASVQDLFAAAHRFQIPSIFTIC
VSFLQKRLCLSNCLAVFRLGLLLDCARLAVAARDFICAHFTLVARDADFLGLSADELIAI
ISSDGLNVEKEEAVFEAVMRWAGSGDAEAQAERQRALPTVFESVRCRLLPRAFLESRVER
HPLVRAQPELLRKVQMVKDAHEGRITTLRKKKKGKDGAGAKEADKGTSKAKAEEDEEAER
ILPGILNDTLRFGMFLQDLIFMISEEGAVAYDPAANECYCASLSNQVPKNHVSLVTKENQ
VFVAGGLFYNEDNKEDPMSAYFLQFDHLDSEWLGMPPLPSPRCLFGLGEALNSIYVVGGR
EIKDGERCLDSVMCYDRLSFKWGESDPLPYVVYGHTVLSHMDLVYVIGGKGSDRKCLNKM
CVYDPKKFEWKELAPMQTARSLFGATVHDGRIIVAAGVTDTGLTSSAEVYSITDNKWAPF
EAFPQERSSLSLVSLVGTLYAIGGFATLETESGELVPTELNDIWRYNEEEKKWEGVLREI
AYAAGATFLPVRLNVLCLTKM

Sequence length

621

Interactions

View interactions

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)

Show/Hide Causal Diseases (2)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
KLHL40-related disorder	Pathogenic	rs397509420	RCV004757124	★★★★★ ★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Nemaline myopathy 8	Likely pathogenic; Pathogenic	rs768335581, rs1697319878, rs2125846068, rs770267750, rs1292866391, rs2125845625, rs1697260724, rs1055019439, rs2125844554, rs2125844563, rs1486566170, rs545767433, rs1440284508, rs924279167, rs573886282 View all (19 more)	RCV001330425 RCV001330424 RCV001526480 RCV001775224 RCV001908401 View all (31 more)	★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Show/Hide Unknown Diseases (1)

Phenotype Name	Clinical Significance	Source	Evidence Score
Unknown / Other Associations ClinVar entries with uncertain/conflicting evidence, and associations from other databases (OMIM, Orphanet, GWAS, etc.) where the gene is not established as causal.
SEVERE CONGENITAL NEMALINE MYOPATHY	—	CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Show/Hide Text Mining Associations (27)

Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Associations from Text Mining Disease associations identified through text mining
Arthrogryposis	Arthrogryposis multiplex congenita	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of lung	Pulmonary hypoplasia	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Congenital myopathy (disorder)	Congenital myopathy	BEFREE	31360996		★★★★★ ★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Deglutition disorder	Pubtator	35379254	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Facial paralysis	Facial paralysis	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Myofibrillar Myopathy	Myofibrillar myopathy	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Myopathies Nemaline	Nemaline myopathy	Pubtator	27528495, 32352246, 35379254	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Myopathies, Nemaline	Myopathy	BEFREE	23746549, 24960163, 25721947, 26754003, 27528495, 30990797, 31360996		★★★★★ ★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	24960163, 26754003, 31360996		★★★★★ ★☆☆☆☆ Found in Text Mining only
Myotonia Congenita	Myotonia congenita	Pubtator	32352246	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
NEMALINE MYOPATHY 8	Nemaline myopathy	UNIPROT_DG	23746549, 26754003, 27528495, 27762439		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEMALINE MYOPATHY 8	Nemaline myopathy	CLINVAR_DG	23746549, 27528495, 27762439		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEMALINE MYOPATHY 8	Nemaline myopathy	GENOMICS_ENGLAND_DG	23746549, 25721947		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEMALINE MYOPATHY 8	Nemaline myopathy	CLINGEN_DG	23746549, 24960163, 26754003, 27528495, 28973083		★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEMALINE MYOPATHY 8	Nemaline myopathy	CTD_human_DG			★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Neuromuscular Diseases	Neuromuscular disease	Pubtator	26578207, 32352246	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Neuromuscular Diseases	Neuromuscular Diseases	BEFREE	27762439		★★★★★ ★☆☆☆☆ Found in Text Mining only
Pena-Shokeir syndrome type I	Pena Shokeir syndrome	BEFREE	27762439		★★★★★ ★☆☆☆☆ Found in Text Mining only
Pena-Shokeir syndrome type I	Pena Shokeir syndrome	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Penis agenesis	Penis Agenesis	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Scoliosis	Scoliosis	Pubtator	25428687	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Severe congenital nemaline myopathy	Congenital Nemaline Myopathy	Orphanet			★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	32931492	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only

KLHL40 (kelch like family member 40)