FRMD1

Chr 6AR

FERM domain containing 1

Also known as: bA164L23.1

NCBI Gene: 79981 ENSG00000153303 UniProt: Q8N878 OMIM: 609245

The FRMD1 protein is predicted to regulate hippo signaling and localizes to the cytoskeleton and apical plasma membrane. Mutations cause Chudley-McCullough syndrome, characterized by early-onset sensorineural hearing loss and brain malformations including polymicrogyria and cerebellar hypoplasia. The condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM

Predicted to enable protein sequestering activity. Predicted to be involved in positive regulation of hippo signaling. Predicted to be active in cell-cell junction and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Chudley-McCullough syndromeMIM #604213

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Chudley-McCullough syndrome; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.30

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.30LOEUF

pLI 0.000

Z-score 0.42

OE 0.91 (0.65–1.30)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.09Z-score

OE missense 1.01 (0.93–1.11)

348 obs / 343.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.91 (0.65–1.30)

0≤0.351.4

Missense OE?1.01 (0.93–1.11)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 22 / 24.2Missense obs/exp: 348 / 343.4Syn Z: -1.07

Background carrier burden — how many people carry a rare variant somewhere in FRMD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 38

927 rare PASS variants

Rare truncating (LoF)

1 in 430

165 rare PASS variants

Rare synonymous (reference)

1 in 80

404 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FRMD1. 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)	~556k	1 in 63	1 in 650
South Asian	~43k	1 in 34	1 in 430
Remaining (unassigned)	~30k	1 in 32	1 in 460
European (Finnish)	~27k	1 in 140	1 in 710
Admixed American	~22k	1 in 36	1 in 480
African / African American	~21k	1 in 37	1 in 430
East Asian	~20k	1 in 62	1 in 640
Ashkenazi Jewish	~13k	1 in 140	1 in 2,100
Middle Eastern	~2,884	1 in 30	1 in 400

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 11 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 11.? see exons ↓