HIPK4

protein-coding

homeodomain interacting protein kinase 4

Gene summary

This gene encodes a member of the homeodomain interacting protein kinase (HIPK) family of proteins. While other members of this family are found throughout vertebrates, this member is present only in mammals. Compared to other members of this family, the encoded protein lacks a nuclear localization signal and a C-terminal autoinhibitory domain. The encoded protein exhibits kinase activity and may phosphorylate the tumor suppressor protein p53. [provided by RefSeq, Jul 2016]

MANE transcript

NM_144685.5

Inheritance

ClinVar variants

P:1U:98B:12

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr19:40,379,271-40,390,181

External References & Databases

Ensembl (ENSG00000160396)

Transcript & Mutation Effects

hg38 • Region Span ~10.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

male infertility with azoospermia or oligozoospermia due to single gene mutationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0018393

Submitter: King Faisal Specialist Hospital and Research Center

Alhathal et al., 2020 (PMID: 32719396) reported a missense variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Moderate with total score of 8. Single-variant analysis (3 points), experimental evidence: Animal model (4 points) and testicular expression (1 points) (PMID: 32163033).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HIPK4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 101

not providedTotal: 5

Prostate cancerTotal: 1

Male infertilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144685.5. 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			95 clinvar	8 clinvar	3 clinvar	106
nonsense						0
start loss		1 clinvar				1
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	98	8	4	111

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144685.5	RefSeq	NP_653286.2	4	MANE Select
ENST00000291823.3	Ensembl	ENSP00000291823.1	4	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cellular senescence - Homo sapiens (human)

Biological Process

histone phosphorylation
peptidyl-serine phosphorylation
protein autophosphorylation
regulation of signal transduction by p53 class mediator

Molecular Function

protein serine/threonine kinase activity
protein binding
ATP binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000291823
Coding exons: 4
Length: 10917
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125748
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	336	404	0.831	0.0000277	4022
Missense (PolyPhen)		109	171.15	0.63686		1817
Synonymous	-0.203	178	175	1.02	0.0000127	1255
Loss of Function	2.08	11	21.4	0.515	0.00000117	219

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00020	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000053	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protein kinase that phosphorylates human TP53 at Ser-9, and thus induces TP53 repression of BIRC5 promoter (By similarity). May act as a corepressor of transcription factors (Potential). {ECO:0000250, ECO:0000305}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.560
RVIS EVS: -0.08
RVIS percentile EVS: 47.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.744

Gene Damage Prediction

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