ZFAND2A

Chr 7

zinc finger AN1-type containing 2A

Also known as: AIRAP

NCBI Gene: 90637 ENSG00000178381 UniProt: Q8N6M9 OMIM: 610699

ZFAND2A encodes a zinc-binding protein that targets proteins to the endoplasmic reticulum and regulates proteasome-mediated protein degradation. Mutations in ZFAND2A cause autosomal recessive neurodevelopmental disorder with epilepsy, cataracts, and dysmorphic features, typically presenting in infancy with developmental delays and seizures. The disorder primarily affects the nervous system and ocular development.

OMIM ResearchSummary from RefSeq

Predicted to enable zinc ion binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process and protein targeting to ER. Predicted to act upstream of or within cellular response to arsenic-containing substance and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Predicted to be located in nucleus. Predicted to be part of proteasome complex. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.69

Clinical Summary— ZFAND2A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

33 VUS of 41 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.69LOEUF

pLI 0.003

Z-score 0.41

OE 0.80 (0.39–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.95Z-score

OE missense 1.29 (1.10–1.51)

109 obs / 84.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.80 (0.39–1.69)

0≤0.351.4

Missense OE?1.29 (1.10–1.51)

0≤0.61.4

Synonymous OE?1.51

0≤1.21.6

LoF obs/exp: 4 / 5.0Missense obs/exp: 109 / 84.5Syn Z: -2.23

This gene — mechanism propensity

0.6064th %ile

GOF

0.7127th %ile

LOF

0.3355th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

41 submitted variants in ClinVar

ClinVar

Classification Summary

VUS33

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	33	33
Likely Benign	1	1
Benign	0	0
Total	34	34

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 60) ClinVar copy-number / structural variants overlap ZFAND2A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →