KHSRP

protein-coding

KH-type splicing regulatory protein, the group of MicroRNA protein coding host genes

Gene summary

The KHSRP gene encodes a multifunctional RNA-binding protein implicated in a variety of cellular processes, including transcription, alternative pre-mRNA splicing, and mRNA localization (Min et al., 1997 [PubMed 9136930]; Gherzi et al., 2004 [PubMed 15175153]).[supplied by OMIM, Apr 2010]

MANE transcript

NM_001366299.1

Inheritance

—

ClinVar variants

U:77B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:6,413,102-6,424,811

External References & Databases

Ensembl (ENSG00000088247)

Transcript & Mutation Effects

hg38 • Region Span ~11.7 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 KHSRP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001366299.1. 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			6 clinvar	3 clinvar	3 clinvar	12
missense			62 clinvar			62
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	77	3	3	83

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001366299.1	RefSeq	NP_001353228.1	19	MANE Select
ENST00000600480.2	Ensembl	ENSP00000471146.2	19	MANE Select
NM_001366300.1	RefSeq	NP_001353229.1	20	Standard
NM_003685.3	RefSeq	NP_003676.2	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Preimplantation Embryo
KSRP (KHSRP) binds and destabilizes mRNA
Metabolism of RNA
Regulation of mRNA stability by proteins that bind AU-rich elements

Biological Process

RNA splicing, via transesterification reactions
regulation of transcription, DNA-templated
mRNA processing
mRNA catabolic process
RNA splicing

Molecular Function

DNA binding
RNA binding
protein binding
mRNA 3'-UTR AU-rich region binding

Cellular Component

exosome (RNase complex)
nucleoplasm
cytosol
cytoplasmic stress granule
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398148
Coding exons: 20
Length: 11447
Individuals with no LoFs: 124606
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 124607
p: 0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.83	173	384	0.450	0.0000237	4524
Missense (PolyPhen)		45	155.16	0.29003		1703
Synonymous	-1.95	193	161	1.20	0.0000122	1454
Loss of Function	5.73	0	38.2	0.00	0.00000186	446

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single- stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'- UTR, possibly by recruiting degradation machinery to ARE- containing mRNAs. {ECO:0000250, ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:8940189, ECO:0000269|PubMed:9136930}.;

Recessive Scores

pRec: 0.155

Intolerance Scores

LoFtool: 0.190
RVIS EVS: -0.69
RVIS percentile EVS: 15.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.995

Gene Damage Prediction

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