ATF7IP2

Chr 16

activating transcription factor 7 interacting protein 2

Also known as: MCAF2

NCBI Gene: 80063 ENSG00000166669 UniProt: Q5U623 OMIM: 613645

The protein functions as a transcriptional recruiter that couples transcription factors to general transcription machinery and modulates chromatin formation, acting as either an activator or repressor depending on context. Mutations in this gene cause autosomal recessive intellectual disability with seizures and microcephaly, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants, suggesting some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of DNA-templated transcription. Predicted to be part of transcription regulator complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.47

Clinical Summary— ATF7IP2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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ClinVar Variants

100 VUS of 131 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.158

Z-score 3.67

OE 0.25 (0.14–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-1.32Z-score

OE missense 1.20 (1.11–1.30)

409 obs / 340.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.25 (0.14–0.47)

0≤0.351.4

Missense OE?1.20 (1.11–1.30)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 7 / 27.9Missense obs/exp: 409 / 340.5Syn Z: -1.52

ClinVar Variant Classifications

131 submitted variants in ClinVar

ClinVar

Classification Summary

VUS100

Likely Benign14

100

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	2	98	0	100
Likely Benign	0	13	1	14
Benign	0	0	0	0
Total	2	111	1	114

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 52) ClinVar copy-number / structural variants overlap ATF7IP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →