KLHL41 (kelch like family member 41)

Gene

• Entrez ID: 10324
• Gene name: Kelch like family member 41
• Gene symbol: KLHL41
• Synonyms (NCBI Gene): KBTBD10, Krp1, SARCOSIN
• Chromosome: 2
• Chromosome location: 2q31.1
• Summary: This gene is a member of the kelch-like family. The encoded protein contains a BACK domain, a BTB/POZ domain, and 5 Kelch repeats. This protein is thought to function in skeletal muscle development and maintenance. Mutations in this gene have been associa

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs730882235	A>-	Pathogenic, likely-pathogenic	Coding sequence variant, frameshift variant
rs730882257	T>ACTC	Pathogenic	Inframe insertion, coding sequence variant
rs730882258	AGGAAATA>-	Pathogenic	Coding sequence variant, frameshift variant
rs730882259	AAG>-	Pathogenic	Inframe deletion, coding sequence variant
rs730882260	C>T	Pathogenic	Missense variant, coding sequence variant
rs775513051	->A,AAAAAAA,AAAAAAAAAAA	Pathogenic	Coding sequence variant, frameshift variant
rs1131691443	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs1247404453	TTACTTCC>-	Pathogenic	Coding sequence variant, frameshift variant
rs1288106608	A>-,AA	Pathogenic	Frameshift variant, coding sequence variant
rs1574349073	ATGAGAAAAAATTCATCGATTGCAC>TGTCA	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1574349645	TGACACAGCA>-	Pathogenic	Coding sequence variant, frameshift variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001726	Component	Ruffle	IEA
GO:0005515	Function	Protein binding	IPI	23414517, 25416956, 30986853, 32296183, 32814053
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	19424503
GO:0005737	Component	Cytoplasm	IEA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	24268659
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IBA
GO:0005856	Component	Cytoskeleton	IEA
GO:0005856	Component	Cytoskeleton	ISS
GO:0005886	Component	Plasma membrane	IDA
GO:0006941	Process	Striated muscle contraction	TAS	9655184
GO:0016020	Component	Membrane	IEA
GO:0016529	Component	Sarcoplasmic reticulum	IEA
GO:0016567	Process	Protein ubiquitination	IDA	15983046
GO:0030239	Process	Myofibril assembly	IEA
GO:0030239	Process	Myofibril assembly	ISS
GO:0031143	Component	Pseudopodium	IEA
GO:0031430	Component	M band	IBA
GO:0031430	Component	M band	IEA
GO:0031430	Component	M band	ISS
GO:0031463	Component	Cul3-RING ubiquitin ligase complex	IBA
GO:0031463	Component	Cul3-RING ubiquitin ligase complex	IDA	15983046
GO:0031463	Component	Cul3-RING ubiquitin ligase complex	IEA
GO:0033017	Component	Sarcoplasmic reticulum membrane	IBA
GO:0033017	Component	Sarcoplasmic reticulum membrane	IDA	24268659
GO:0033017	Component	Sarcoplasmic reticulum membrane	IEA
GO:0035914	Process	Skeletal muscle cell differentiation	IEA
GO:0035914	Process	Skeletal muscle cell differentiation	ISS
GO:0042995	Component	Cell projection	IEA
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IBA
GO:0045661	Process	Regulation of myoblast differentiation	IBA
GO:0045661	Process	Regulation of myoblast differentiation	IEA
GO:0045661	Process	Regulation of myoblast differentiation	ISS
GO:1990756	Function	Ubiquitin-like ligase-substrate adaptor activity	IBA
GO:2000291	Process	Regulation of myoblast proliferation	IBA
GO:2000291	Process	Regulation of myoblast proliferation	IEA
GO:2000291	Process	Regulation of myoblast proliferation	ISS
GO:2001014	Process	Regulation of skeletal muscle cell differentiation	IBA
GO:2001014	Process	Regulation of skeletal muscle cell differentiation	IEA

Other IDs

• MIM: 607701
• HGNC: 16905
• e!Ensembl: ENSG00000239474

Protein

• UniProt ID: O60662
• Protein name: Kelch-like protein 41 (Kel-like protein 23) (Kelch repeat and BTB domain-containing protein 10) (Kelch-related protein 1) (Sarcosin)
• Protein function: Involved in skeletal muscle development and differentiation. Regulates proliferation and differentiation of myoblasts and plays a role in myofibril assembly by promoting lateral fusion of adjacent thin fibrils into mature, wide myofibrils. Requi
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00651	BTB	23 → 130	BTB/POZ domain	Domain
  PF07707	BACK	135 → 237	BTB And C-terminal Kelch	Domain
  PF01344	Kelch_1	334 → 385	Kelch motif	Repeat
  PF01344	Kelch_1	387 → 434	Kelch motif	Repeat
  PF01344	Kelch_1	437 → 482	Kelch motif	Repeat
  PF01344	Kelch_1	484 → 529	Kelch motif	Repeat

• Tissue specificity: TISSUE SPECIFICITY: Sarcomeric muscle.
• Sequence:

  MDSQRELAEELRLYQSTLLQDGLKDLLDEKKFIDCTLKAGDKSLPCHRLILSACSPYFRE
  YFLSEIDEAKKKEVVLDNVDPAILDLIIKYLYSASIDLNDGNVQDIFALASRFQIPSVFT
  VCVSYLQKRLAPGNCLAILRLGLLLDCPRLAISAREFVSDRFVQICKEEDFMQLSPQELI
  SVISNDSLNVEKEEAVFEAVMKWVRTDKENRVKNLSEVFDCIRFRLMTEKYFKDHVEKDD
  IIKSNPDLQKKIKVLKDAFAGKLPEPSKNAAKTGAGEVNGDVGDEDLLPGYLNDIPRHGM
  FVKDLILLVNDTAAVAYDPTENECYLTALAEQIPRNHSSIVTQQNQIYVVGGLYVDEENK
  DQPLQSYFFQLDSIASEWVGLPPLPSARCLFGLGEVDDKIYVVAGKDLQTEASLDSVLCY
  DPVAAKWNEVKKLPIKVYGHNVISHKGMIYCLGGKTDDKKCTNRVFIFNPKKGDWKDLAP
  MKIPRSMFGVAVHKGKIVIAGGVTEDGLSASVEAFDLTTNKWDVMTEFPQERSSISLVSL
  AGSLYAIGGFAMIQLESKEFAPTEVNDIWKYEDDKKEWAGMLKEIRYASGASCLATRLNL
  FKLSKL

• Sequence length: 606

Pathways

Reactome:

Neddylation
Antigen processing: Ubiquitination & Proteasome degradation

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
KLHL41-related disorder	Likely pathogenic; Pathogenic	rs749464576	RCV003892845	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Nemaline myopathy	Likely pathogenic; Pathogenic	rs730882235	RCV000162159	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Nemaline myopathy 9	Pathogenic; Likely pathogenic	rs779140230, rs2105309832, rs2105312506, rs775513051, rs749464576, rs2105312600, rs754460870, rs730882257, rs730882258, rs730882235, rs730882259, rs730882260, rs2468054831, rs1317318638, rs2468062223, rs2468055198, rs1185815773, rs2468055654, rs2468059698, rs1364684686, rs1247404453, rs1574349645, rs1288106608	RCV001386119 RCV001388342 RCV001383527 RCV001782347 RCV001782348 RCV001963163 RCV001963625 RCV000162074 RCV000162075 RCV000162076 RCV000162077 RCV000162078 RCV002785664 RCV002852451 RCV002848311 RCV002953926 RCV003030516 RCV003155902 RCV003747030 RCV003746284 RCV000685819 RCV000705302 RCV000799899 RCV000800431	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CHILDHOOD-ONSET NEMALINE MYOPATHY	—	Disgenet, Orphanet Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERMEDIATE NEMALINE MYOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOPATHIES, NEMALINE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE CONGENITAL NEMALINE MYOPATHY	—	CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPICAL NEMALINE MYOPATHY	—	Disgenet, Orphanet Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthrogryposis	Arthrogryposis multiplex congenita	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Hypertrophic	Hypertrophic cardiomyopathy	Pubtator	11583900	Associate	★☆☆☆☆ Found in Text Mining only
Childhood-onset nemaline myopathy	Nemaline myopathy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
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 pectus excavatum	Congenital Pectus Excavatum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Generalized limb muscle atrophy	Limb Muscle Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intermediate nemaline myopathy	Nemaline myopathy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma Cutaneous Malignant	Melanoma	Pubtator	34757537	Stimulate	★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myopathies, Nemaline	Myopathy	BEFREE	24268659, 28826497, 30986853, 30990797		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myopathies, Nemaline	Myopathy	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myopathy	Myopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
NEMALINE MYOPATHY 9	Nemaline myopathy	GENOMICS_ENGLAND_DG	24268659		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEMALINE MYOPATHY 9	Nemaline myopathy	CLINGEN_DG	24268659, 28826497, 28939701		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEMALINE MYOPATHY 9	Nemaline myopathy	UNIPROT_DG	24268659		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEMALINE MYOPATHY 9	Nemaline myopathy	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NEMALINE MYOPATHY 9	Nemaline myopathy	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Nemaline Myopathy, Childhood Onset	Nemaline myopathy	ORPHANET_DG	24268659		★☆☆☆☆ Found in Text Mining only
Neonatal Hypotonia	Hypotonia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neuromuscular Diseases	Neuromuscular disease	Pubtator	26578207	Associate	★☆☆☆☆ Found in Text Mining only
Neuromuscular dysphagia	Neuromuscular dysphagia	HPO_DG			★☆☆☆☆ 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
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe congenital nemaline myopathy	Congenital Nemaline Myopathy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Typical nemaline myopathy	Nemaline myopathy	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations