ERICH6B

Chr 13

glutamate rich 6B

Also known as: FAM194B

ERICH6B encodes a protein containing glutamate-rich and leucine-zipper domains that localizes to the centrosome and is involved in centriole duplication and cell cycle regulation. Biallelic mutations cause autosomal recessive primary microcephaly with severe intellectual disability and seizures, typically manifesting from birth. The gene shows very low constraint against loss-of-function variants, consistent with a recessive inheritance pattern where heterozygous carriers are unaffected.

DNmechanismLOEUF 1.07
Clinical SummaryERICH6B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 unique Pathogenic / Likely Pathogenic· 86 VUS of 162 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.23
OE 0.77 (0.561.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.79Z-score
OE missense 0.73 (0.660.81)
250 obs / 343.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.77 (0.561.07)
00.351.4
Missense OE0.73 (0.660.81)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 26 / 33.7Missense obs/exp: 250 / 343.5Syn Z: 1.04
DN
0.6939th %ile
GOF
0.5367th %ile
LOF
0.2971th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

162 submitted variants in ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic1
VUS86
Likely Benign16
54
Pathogenic
1
Likely Pathogenic
86
VUS
16
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
1
0
1
VUS
0
83
3
0
86
Likely Benign
0
9
0
7
16
Benign
0
0
0
0
0
Total092587157

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

View in ClinVar →

Protein Context — Lollipop Plot

ERICH6B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found