ABTB1

Chr 3

ankyrin repeat and BTB domain containing 1

Also known as: BPOZ, BPOZ-2, BTB3, BTBD21, EF1ABP, PP2259

NCBI Gene: 80325 ENSG00000114626 UniProt: Q969K4 OMIM: 608308

This gene encodes a protein with an ankyrin repeat region and two BTB/POZ domains, which are thought to be involved in protein-protein interactions. Expression of this gene is activated by the phosphatase and tensin homolog, a tumor suppressor. Alternate splicing results in three transcript variants. [provided by RefSeq, Mar 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.76

Clinical Summary— ABTB1

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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

100 VUS of 125 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?

0.76LOEUF

pLI 0.000

Z-score 2.51

OE 0.47 (0.30–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.34Z-score

OE missense 0.95 (0.86–1.04)

298 obs / 315.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.30–0.76)

0≤0.351.4

Missense OE?0.95 (0.86–1.04)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 12 / 25.7Missense obs/exp: 298 / 315.2Syn Z: -1.00

This gene — mechanism propensity

0.6743th %ile

GOF

0.73top 25%

LOF

0.2775th %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.

ClinVar Variant Classifications

125 submitted variants in ClinVar

ClinVar

Classification Summary

VUS100

Likely Benign7

100

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	100	0	100
Likely Benign	6	1	7
Benign	0	0	0
Total	106	1	107

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap ABTB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →