KLHL41

kelch like family member 41, the group of Kelch like|BTB domain containing

Basic information

Region (hg38): 2:169509702-169526258

Previous symbols: [ "KBTBD10" ]

Links

ENSG00000239474 ∙ NCBI:10324 ∙ OMIM:607701 ∙ HGNC:16905 ∙ Uniprot:O60662 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nemaline myopathy 9 (Strong), mode of inheritance: AR
• severe congenital nemaline myopathy (Supportive), mode of inheritance: AR
• intermediate nemaline myopathy (Supportive), mode of inheritance: AD
• typical nemaline myopathy (Supportive), mode of inheritance: AD
• childhood-onset nemaline myopathy (Supportive), mode of inheritance: AD
• nemaline myopathy 9 (Moderate), mode of inheritance: AR
• nemaline myopathy 9 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nemaline myopathy 9	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	Craniofacial; Musculoskeletal	24268659

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLHL41 gene.

• Nemaline myopathy 9 (14 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL41 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	66	1	69
missense		1	138	7	2	148
nonsense	6	1	1			8
start loss						0
frameshift	8	4				12
inframe indel			2			2
splice donor/acceptor (+/-2bp)		1		2		3
splice region			1	4	2	7
non coding				25	9	34
Total	14	7	143	100	12

Highest pathogenic variant AF is 0.0000197

Variants in KLHL41

This is a list of pathogenic ClinVar variants found in the KLHL41 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-169509786-C-T		not specified • Nemaline myopathy 9	Benign (Feb 01, 2024)
2-169509792-G-A		Nemaline myopathy 9	Uncertain significance (Dec 09, 2021)
2-169509793-G-A		Nemaline myopathy 9 • KLHL41-related disorder	Benign/Likely benign (Jan 10, 2024)
2-169509800-G-A		Nemaline myopathy 9	Uncertain significance (Jan 21, 2020)
2-169509801-C-T		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
2-169509811-G-C		Nemaline myopathy 9	Likely benign (Sep 13, 2023)
2-169509828-C-G		Nemaline myopathy 9	Uncertain significance (Jul 01, 2022)
2-169509830-C-T		Nemaline myopathy 9	Uncertain significance (Mar 22, 2022)
2-169509839-G-C		Nemaline myopathy 9	Uncertain significance (Mar 13, 2022)
2-169509843-G-C		Nemaline myopathy 9	Uncertain significance (Oct 18, 2022)
2-169509851-G-A		Nemaline myopathy 9	Uncertain significance (Mar 29, 2022)
2-169509851-G-T		Nemaline myopathy 9	Uncertain significance (Jan 27, 2022)
2-169509856-C-G		Nemaline myopathy 9	Likely benign (Jul 30, 2022)
2-169509861-ATGAGAAAAAATTCATCGATTGCAC-TGTCA			Likely pathogenic (Mar 06, 2020)
2-169509877-C-T		Nemaline myopathy 9	Likely benign (Feb 04, 2022)
2-169509879-A-G		Nemaline myopathy 9	Uncertain significance (Sep 21, 2021)
2-169509880-T-C		Nemaline myopathy 9	Likely benign (Mar 18, 2022)
2-169509913-T-C		Nemaline myopathy 9	Likely benign (Aug 01, 2022)
2-169509923-T-C		Nemaline myopathy 9	Likely benign (Dec 20, 2021)
2-169509924-T-C		Nemaline myopathy 9	Uncertain significance (Feb 13, 2019)
2-169509931-G-T		Inborn genetic diseases	Uncertain significance (Jun 05, 2023)
2-169509931-GTCAGC-G		Nemaline myopathy 9	Pathogenic (Oct 17, 2022)
2-169509942-GTCCTTACT-G		Nemaline myopathy 9	Pathogenic (Jun 16, 2017)
2-169509948-AC-CT		Nemaline myopathy 9	Uncertain significance (Aug 30, 2023)
2-169509953-C-T		Nemaline myopathy 9	Uncertain significance (Oct 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLHL41	protein_coding	protein_coding	ENST00000284669	6	16561

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000111	0.990	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.887	282	327	0.862	0.0000172	3991
Missense in Polyphen		84	111.32	0.75457		1324
Synonymous	1.17	103	119	0.863	0.00000629	1179
Loss of Function	2.27	10	21.3	0.469	9.84e-7	299

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000307	0.000304
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000247	0.000246
Middle Eastern	0.000163	0.000163
South Asian	0.0000984	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. Required for pseudopod elongation in transformed cells. {ECO:0000250|UniProtKB:A2AUC9}.
• Disease: DISEASE: Nemaline myopathy 9 (NEM9) [MIM:615731]: An autosomal recessive form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM9 phenotype is highly variable, ranging from death in infancy due to lack of antigravity movements, to slowly progressive distal muscle weakness with preserved ambulation later in childhood. {ECO:0000269|PubMed:24268659}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• rvis_EVS: 0.2
• rvis_percentile_EVS: 67.3

Haploinsufficiency Scores

• pHI: 0.875
• hipred: N
• hipred_score: 0.455
• ghis: 0.517

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: Klhl41
• Phenotype: growth/size/body region phenotype; muscle 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); limbs/digits/tail phenotype

Zebrafish Information Network

• Gene name: klhl41a
• Affected structure: skeletal muscle
• Phenotype tag: abnormal
• Phenotype quality: refractivity

Gene ontology

• Biological process: striated muscle contraction;protein ubiquitination;myofibril assembly;regulation of lateral pseudopodium assembly;skeletal muscle cell differentiation;post-translational protein modification;sarcomere organization;regulation of myoblast differentiation;skeletal muscle fiber development;regulation of myoblast proliferation;regulation of skeletal muscle cell differentiation
• Cellular component: ruffle;nucleus;cytoplasm;endoplasmic reticulum membrane;cytosol;cytoskeleton;plasma membrane;pseudopodium;M band;Cul3-RING ubiquitin ligase complex;sarcoplasmic reticulum membrane
• Molecular function: protein binding