ID4

Chr 6

inhibitor of DNA binding 4

Also known as: IDB4, bHLHb27

NCBI Gene: 3400ENSG00000172201UniProt: P47928

This gene encodes a member of the inhibitor of DNA binding (ID) protein family. The encoded protein lacks DNA binding ability, and instead regulates gene expression through binding to and inhibiting basic helix-loop-helix transcription factors. This protein has been implicated in the regulation of diverse cellular processes that play a role in development and tumorigenesis. [provided by RefSeq, Aug 2017]

44
ClinVar variants
13
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— ID4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 30 VUS of 44 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.83LOEUF
pLI 0.031
Z-score 0.23
OE 0.84 (0.32–1.83)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.86Z-score
OE missense 1.31 (1.09–1.59)
77 obs / 58.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.84 (0.32–1.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.31 (1.09–1.59)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.2.00
0≤1.21.6
LoF obs/exp: 2 / 2.4Missense obs/exp: 77 / 58.6Syn Z: -4.16

ClinVar Variant Classifications

44 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
VUS30
Benign1
13
Pathogenic
30
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
0
0
0
VUS
0
30
0
0
30
Likely Benign
0
0
0
0
0
Benign
0
0
1
0
1
Total03014044

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

View in ClinVar →

Protein Context — Lollipop Plot

ID4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Menke-Hennekam syndrome; delineation of domain-specific subtypes with distinct clinical and DNA methylation profiles.
Haghshenas S et al.·HGG Adv
2024
Inhibitor of differentiation 4 (ID4): From development to cancer.
Patel D et al.·Biochim Biophys Acta
2015Review
Differential expression of ID4 and its association with TP53 mutation, SOX2, SOX4 and OCT-4 expression levels.
Galatro TF et al.·PLoS One
2013
Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer.
Baker LA et al.·Breast Cancer Res
2020
The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1.
Pruszko M et al.·EMBO Rep
2017
Systematic review of genome-wide association studies on susceptibility to endometriosis.
Cardoso JV et al.·Eur J Obstet Gynecol Reprod Biol
2020Meta-analysis
CDC42 as an epigenetic regulator of ID4 in triple-negative breast tumors.
Nasif D et al.·Breast Cancer
2022
FGFR1 variants contributed to families with tooth agenesis.
Yao S et al.·Hum Genomics
2023
[Clinical Significance of ID4 Gene Mehtylation in Demethylation-Treated MDS Cell Line and 2 MDS Patients].
Kang HY et al.·Zhongguo Shi Yan Xue Ye Xue Za Zhi
2015Cohort
Epigenetic regulation of ID4 in the determination of the BRCAness phenotype in breast cancer.
Branham MT et al.·Breast Cancer Res Treat
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools