KLHL40

kelch like family member 40, the group of BTB domain containing|Kelch like

Basic information

Region (hg38): 3:42685537-42692544

Previous symbols: [ "KBTBD5" ]

Links

ENSG00000157119 ∙ NCBI:131377 ∙ OMIM:615340 ∙ HGNC:30372 ∙ Uniprot:Q2TBA0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nemaline myopathy 8 (Definitive), mode of inheritance: AR
• nemaline myopathy 8 (Strong), mode of inheritance: AR
• nemaline myopathy 8 (Moderate), mode of inheritance: AR
• severe congenital nemaline myopathy (Supportive), mode of inheritance: AR
• nemaline myopathy 8 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nemaline myopathy 8	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	23746549

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLHL40 gene.

• Nemaline_myopathy_8 (464 variants)
• Inborn_genetic_diseases (109 variants)
• not_provided (89 variants)
• not_specified (20 variants)
• KLHL40-related_disorder (17 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL40 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000152393.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	142	5	151
missense	3	9	281	12	3	308
nonsense	9	6				15
start loss						0
frameshift	9	2	3			14
splice donor/acceptor (+/-2bp)	2	5			1	8
Total	23	22	288	154	9

Highest pathogenic variant AF is 0.0000591972

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLHL40	protein_coding	protein_coding	ENST00000287777	6	7026

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000354	0.947	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0218	420	421	0.997	0.0000282	4024
Missense in Polyphen		125	126.26	0.99003		1243
Synonymous	0.143	190	193	0.987	0.0000142	1285
Loss of Function	1.83	12	21.0	0.570	8.98e-7	250

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000150	0.000149
Ashkenazi Jewish	0.00	0.00
East Asian	0.000336	0.000217
Finnish	0.0000478	0.0000462
European (Non-Finnish)	0.000127	0.000105
Middle Eastern	0.000336	0.000217
South Asian	0.00	0.00
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: 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, thereby regulating the activity of the E2F:DP transcription factor complex (By similarity). Promotes stabilization of LMOD3 by acting as a negative regulator of LMOD3 ubiquitination; the molecular process by which it negatively regulates ubiquitination of LMOD3 is however unclear (By similarity). {ECO:0000250|UniProtKB:Q9D783, ECO:0000269|PubMed:23746549}.

Intolerance Scores

• rvis_EVS: -0.91
• rvis_percentile_EVS: 10.12

Haploinsufficiency Scores

• pHI: 0.502
• hipred: Y
• hipred_score: 0.707
• ghis: 0.545

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Klhl40
• Phenotype: muscle phenotype; cellular phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: klhl40b
• Affected structure: skeletal muscle
• Phenotype tag: abnormal
• Phenotype quality: loose

Gene ontology

• Biological process: negative regulation of protein ubiquitination;positive regulation of protein ubiquitination;negative regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;skeletal muscle fiber development;skeletal muscle fiber differentiation
• Cellular component: cytoplasm;Cul3-RING ubiquitin ligase complex;A band;I band