ANKRD30A

Chr 10

ankyrin repeat domain 30A

Also known as: NY-BR-1

NCBI Gene: 91074 ENSG00000148513 UniProt: Q9BXX3

This gene encodes a DNA-binding transcription factor that is uniquely expressed in mammary epithelium and testis. The gene shows very low constraint against loss-of-function variants (pLI near zero), and no pediatric neurological disorders have been definitively associated with ANKRD30A mutations to date. Current evidence suggests this gene may be primarily relevant to breast cancer rather than neurogenetic conditions.

Summary from RefSeq

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Active trials

Pubs (1 yr)

P/LP submissions

P/LP missense

1.26

LOEUF

Multiple*

Mechanism· predicted

Clinical Summary— ANKRD30A

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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

8 unique Pathogenic / Likely Pathogenic· 170 VUS of 212 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

1.26LOEUF

pLI 0.000

Z-score -0.23

OE 1.03 (0.85–1.26)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

-2.83Z-score

OE missense 1.33 (1.25–1.41)

778 obs / 585.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios

LoF OE1.03 (0.85–1.26)

0≤0.351.4

Missense OE1.33 (1.25–1.41)

0≤0.61.4

Synonymous OE1.20

0≤1.21.6

LoF obs/exp: 67 / 65.0Missense obs/exp: 778 / 585.6Syn Z: -2.27

0.75top 25%

GOF

0.78top 25%

LOF

0.3067th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction 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.