KLHL15

kelch like family member 15, the group of Kelch like|BTB domain containing

Basic information

Region (hg38): X:23983716-24027186

Links

ENSG00000174010 ∙ NCBI:80311 ∙ OMIM:300980 ∙ HGNC:29347 ∙ Uniprot:Q96M94 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, X-linked 103 (Strong), mode of inheritance: XL
• intellectual disability, X-linked 103 (Limited), mode of inheritance: AD
• intellectual disability, X-linked 103 (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 103	XL	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; Neurologic	24817631; 25644381

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KLHL15 gene.

• not_provided (42 variants)
• not_specified (30 variants)
• Intellectual_disability,_X-linked_103 (13 variants)
• KLHL15-related_disorder (6 variants)
• Abnormal_brain_morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLHL15 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000030624.3. 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			1	18	3	22
missense	1	1	59	2		63
nonsense			1			1
start loss						0
frameshift	1		1			2
splice donor/acceptor (+/-2bp)						0
Total	2	1	62	20	3

Highest pathogenic variant AF is 9.106282e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KLHL15	protein_coding	protein_coding	ENST00000328046	2	43467

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00578	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.69	84	247	0.340	0.0000196	4025
Missense in Polyphen		19	84.289	0.22542		1313
Synonymous	-0.105	99	97.7	1.01	0.00000831	1152
Loss of Function	3.63	0	15.3	0.00	0.00000126	247

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Substrate-specific adapter for CUL3 E3 ubiquitin-protein ligase complex (PubMed:14528312). Acts as an adapter for CUL3 to target the serine/threonine-protein phosphatase 2A (PP2A) subunit PPP2R5B for ubiquitination and subsequent proteasomal degradation, thus promoting exchange with other regulatory subunits (PubMed:23135275). Acts as an adapter for CUL3 to target the DNA- end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, plays a key role in DNA damage response, favoring DNA double-strand repair through error-prone non- homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:27561354). {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:23135275, ECO:0000269|PubMed:27561354}.
• Disease: DISEASE: Mental retardation, X-linked 103 (MRX103) [MIM:300982]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:24817631, ECO:0000269|PubMed:25644381}. Note=The disease may be caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.111

Intolerance Scores

• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• pHI: 0.602
• hipred: Y
• hipred_score: 0.783
• ghis: 0.607

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Klhl15

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;protein ubiquitination;nuclear protein quality control by the ubiquitin-proteasome system;negative regulation of double-strand break repair via homologous recombination
• Cellular component: nucleus;Cul3-RING ubiquitin ligase complex
• Molecular function: protein binding