INCA1

protein-coding

inhibitor of CDK, cyclin A1 interacting protein 1

Gene summary

Enables cyclin binding activity; cyclin-dependent protein serine/threonine kinase inhibitor activity; and identical protein binding activity. Acts upstream of or within negative regulation of cyclin-dependent protein serine/threonine kinase activity. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001394789.1

Inheritance

—

ClinVar variants

U:37B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.23

Max pathogenic AF

—

Genomic locus

chr17:4,988,130-4,997,610

External References & Databases

Ensembl (ENSG00000196388)

Transcript & Mutation Effects

hg38 • Region Span ~9.5 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 INCA1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 37

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394789.1. 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				1 clinvar		1
missense			35 clinvar	3 clinvar		38
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	37	4	0	41

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394789.1	RefSeq	NP_001381718.1	6	MANE Select
ENST00000695324.1	Ensembl	ENSP00000511805.1	6	MANE Select
NM_001167985.2	RefSeq	NP_001161457.1	6	Standard
NM_001167986.2	RefSeq	NP_001161458.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of cell population proliferation
negative regulation of cyclin-dependent protein serine/threonine kinase activity
positive regulation of apoptotic signaling pathway

Molecular Function

cyclin-dependent protein serine/threonine kinase inhibitor activity
protein binding
cyclin binding
protein-containing complex binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396829
Coding exons: 6
Length: 9481
Individuals with no LoFs: 125682
Homozygous LoFs: 0
Heterozygous LoFs: 66
Defined: 125748
p: 0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.229	127	134	0.944	0.00000691	1531
Missense (PolyPhen)		29	36.291	0.79911		403
Synonymous	0.384	45	48.4	0.930	0.00000240	465
Loss of Function	-0.736	15	12.2	1.23	6.17e-7	131

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.00061	0.00061	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00046	0.00046	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to CDK2-bound cyclins and inhibits the kinase activity of CDK2; binding to cyclins is critical for its function as CDK inhibitor (PubMed:21540187). Inhibits cell growth and cell proliferation and may play a role in cell cycle control (By similarity). Required for ING5-mediated regulation of S-phase progression, enhancement of Fas-induced apoptosis and inhibition of cell growth (By similarity). {ECO:0000250|UniProtKB:Q6PKN7, ECO:0000269|PubMed:21540187}.;

Intolerance Scores

LoFtool: 0.265
RVIS EVS: 0.22
RVIS percentile EVS: 68.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.148

Gene Damage Prediction

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