ERICH6B

Chr 13

glutamate rich 6B

Also known as: FAM194B

NCBI Gene: 220081 ENSG00000165837 UniProt: Q5W0A0

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.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.07

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.000

Z-score 1.23

OE 0.77 (0.56–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.79Z-score

OE missense 0.73 (0.66–0.81)

250 obs / 343.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.77 (0.56–1.07)

0≤0.351.4

Missense OE?0.73 (0.66–0.81)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 26 / 33.7Missense obs/exp: 250 / 343.5Syn Z: 1.04

Background carrier burden — how many people carry a rare variant somewhere in ERICH6B?

gnomAD v4 · ~700k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 45

811 rare PASS variants

Rare truncating (LoF)

1 in 600

151 rare PASS variants

Rare synonymous (reference)

1 in 89

309 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ERICH6B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~540k	1 in 68	1 in 580
South Asian	~40k	1 in 58	1 in 580
Remaining (unassigned)	~29k	1 in 38	1 in 370
European (Finnish)	~25k	1 in 240	1 in 1,100
African / African American	~21k	1 in 40	1 in 780
East Asian	~18k	1 in 80	1 in 230
Admixed American	~18k	1 in 59	1 in 380
Ashkenazi Jewish	~13k	1 in 370	≈ 1 in 13,000
Middle Eastern	~2,852	1 in 61	≈ 1 in 570

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓