KLHL31

protein-coding

kelch like family member 31, the group of Kelch like|BTB domain containing

Gene summary

Involved in negative regulation of JNK cascade and negative regulation of protein phosphorylation. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

KBTBD1

MANE transcript

NM_001003760.5

Inheritance

—

ClinVar variants

U:80B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr6:53,647,916-53,665,756

External References & Databases

Ensembl (ENSG00000124743)

Transcript & Mutation Effects

hg38 • Region Span ~17.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KLHL31 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 82

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001003760.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			79 clinvar	4 clinvar		83
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	80	5	0	85

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001003760.5	RefSeq	NP_001003760.2	2	MANE Select
ENST00000370905.4	Ensembl	ENSP00000359942.3	2	MANE Select
ENST00000407079.1	Ensembl	ENSP00000384644.1	2	Standard
ENST00001139948.1	Ensembl	ENSP00000809795.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
klhl31	Danio rerio	Structure: pericardial cavity Quality: edematous abnormal

Gene / Model

Organism

Observed Phenotype

klhl31

Danio rerio

Structure: pericardial cavity

Quality: edematous

abnormal

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370905
Coding exons: 2
Length: 17808
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125748
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.765	319	360	0.886	0.0000178	4139
Missense (PolyPhen)		111	139.8	0.79401		1637
Synonymous	0.553	139	148	0.942	0.00000744	1259
Loss of Function	1.87	12	21.3	0.563	0.00000117	242

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.00033	0.00033	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00020	0.00020	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions. Overexpression inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE). {ECO:0000269|PubMed:18719355}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.474
RVIS EVS: 0.02
RVIS percentile EVS: 55.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.128

Gene Damage Prediction

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