CDKN2AIP

protein-coding

CDKN2A interacting protein

Gene summary

The protein encoded by this gene regulates the DNA damage response through several different signaling pathways. One such pathway is the p53-HDM2-p21(WAF1) pathway, which is critical to the DNA damage response. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

MANE transcript

NM_017632.4

Inheritance

—

ClinVar variants

U:91B:1

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr4:183,444,635-183,449,064

External References & Databases

Ensembl (ENSG00000168564)

Transcript & Mutation Effects

hg38 • Region Span ~4.4 kb

Loading mutation effect viewer...

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 CDKN2AIP variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 87

not providedTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017632.4. 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
missense			91 clinvar			91
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	91	1	0	92

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_017632.4	RefSeq	NP_060102.1	3	MANE Select
ENST00000504169.2	Ensembl	ENSP00000427108.1	3	MANE Select
NM_001317343.2	RefSeq	NP_001304272.1	3	Standard
ENST00000302350.4	Ensembl	ENSP00000303788.4	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cdkn2aip	Danio rerio	Structure: definitive hemopoiesis Quality: decreased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

cdkn2aip

Danio rerio

Structure: definitive hemopoiesis

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cellular response to DNA damage stimulus
positive regulation of signal transduction
positive regulation of cell growth
negative regulation of cell growth
regulation of protein stability

Molecular Function

p53 binding
RNA binding
protein binding

Cellular Component

granular component
nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000504169
Coding exons: 3
Length: 3608
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.539	271	297	0.912	0.0000141	3706
Missense (PolyPhen)		16	36.747	0.43541		507
Synonymous	0.0566	121	122	0.993	0.00000614	1200
Loss of Function	3.63	2	19.1	0.104	9.56e-7	258

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	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates DNA damage response in a dose-dependent manner through a number of signaling pathways involved in cell proliferation, apoptosis and senescence. {ECO:0000269|PubMed:15109303, ECO:0000269|PubMed:24825908}.;

Recessive Scores

pRec: 0.0986

Intolerance Scores

LoFtool: 0.0138
RVIS EVS: -0.49
RVIS percentile EVS: 22.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: N
Indispensability score: 0.166

Gene Damage Prediction

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