APIP

protein-coding

APAF1 interacting protein

Gene summary

Enables identical protein binding activity; methylthioribulose 1-phosphate dehydratase activity; and zinc ion binding activity. Involved in several processes, including obsolete L-methionine salvage from methylthioadenosine; protein homotetramerization; and pyroptotic inflammatory response. Located in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015957.4

Inheritance

—

ClinVar variants

U:32B:2

Top phenotype

Pyruvate dehydrogenase E3-binding protein deficiency

gnomAD constraint

pLI —, LoF o/e 1.17

Max pathogenic AF

—

Genomic locus

chr11:34,853,094-34,916,379

External References & Databases

Ensembl (ENSG00000149089)

Transcript & Mutation Effects

hg38 • Region Span ~63.3 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 APIP variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 28

not providedTotal: 2

Pyruvate dehydrogenase E3-binding protein deficiencyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015957.4. 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			30 clinvar	2 clinvar		32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	32	2	0	34

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015957.4	RefSeq	NP_057041.2	7	MANE Select
ENST00000395787.4	Ensembl	ENSP00000379133.3	7	MANE Select
ENST00000532428.6	Ensembl	ENSP00000474191.1	5	Standard
ENST00000901543.1	Ensembl	ENSP00000571602.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cysteine and methionine metabolism - Homo sapiens (human)
Methionine De Novo and Salvage Pathway
Metabolism of polyamines
Metabolism of amino acids and derivatives
Methionine salvage pathway

Biological Process

apoptotic process
L-methionine salvage from S-adenosylmethionine
L-methionine salvage from methylthioadenosine
negative regulation of apoptotic process
protein homotetramerization

Molecular Function

protein binding
zinc ion binding
identical protein binding
methylthioribulose 1-phosphate dehydratase activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395787
Coding exons: 7
Length: 63406
Individuals with no LoFs: 125139
Homozygous LoFs: 4
Heterozygous LoFs: 605
Defined: 125748
p: 0.00242

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.785	107	132	0.808	0.00000650	1568
Missense (PolyPhen)		29	35.91	0.80756		446
Synonymous	-0.0528	44	43.6	1.01	0.00000221	436
Loss of Function	-0.549	15	12.9	1.17	5.41e-7	174

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00076	0.00074	rare
Latino/Admixed American	0.00086	0.00084	rare
Ashkenazi Jewish	0.013	0.013	notable
East Asian	0.0011	0.0011	notable
Finnish	0.0020	0.0020	notable
European (Non-Finnish)	0.0029	0.0028	notable
South Asian	0.00093	0.00085	rare
Other	0.0040	0.0039	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the dehydration of methylthioribulose-1- phosphate (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1- phosphate (DK-MTP-1-P). Functions in the methionine salvage pathway, which plays a key role in cancer, apoptosis, microbial proliferation and inflammation. May inhibit the CASP1-related inflammatory response (pyroptosis), the CASP9-dependent apoptotic pathway and the cytochrome c-dependent and APAF1-mediated cell death. {ECO:0000255|HAMAP-Rule:MF_03116, ECO:0000269|PubMed:15262985, ECO:0000269|PubMed:22837397, ECO:0000269|PubMed:23285211, ECO:0000269|PubMed:24367089}.;

Recessive Scores

pRec: 0.120

Intolerance Scores

LoFtool: 0.884
RVIS EVS: 0.68
RVIS percentile EVS: 85.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.370

Gene Damage Prediction

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