FARP1

Chr 13

FERM, ARH/RhoGEF and pleckstrin domain protein 1

Also known as: CDEP, FARP1-IT1, GLCC1, PLEKHC2, PPP1R75

NCBI Gene: 10160 ENSG00000152767 UniProt: Q9Y4F1 OMIM: 602654

The protein functions as a guanine nucleotide exchange factor for RAC1 and promotes dendritic growth, spine formation, and synapse development in neurons. Mutations cause autosomal recessive epilepsy with intellectual disability and behavioral abnormalities, typically presenting in early childhood. The gene is extremely intolerant to loss-of-function variants (pLI near 1.0), indicating that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein containing a FERM (4.2, exrin, radixin, moesin) domain, a Dbl homology domain, and two pleckstrin homology domains. These domains are found in guanine nucleotide exchange factors and proteins that link the cytoskeleton to the cell membrane. The encoded protein functions in neurons to promote dendritic growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.51

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.000

Z-score 4.55

OE 0.35 (0.24–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.84Z-score

OE missense 0.91 (0.85–0.97)

593 obs / 653.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.24–0.51)

0≤0.351.4

Missense OE?0.91 (0.85–0.97)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 20 / 57.1Missense obs/exp: 593 / 653.1Syn Z: -0.77

Background carrier burden — how many people carry a rare variant somewhere in FARP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 22

1,964 rare PASS variants

Rare truncating (LoF)

1 in 170

236 rare PASS variants

Rare synonymous (reference)

1 in 41

874 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FARP1. 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 36	1 in 390
South Asian	~43k	1 in 25	1 in 780
Remaining (unassigned)	~30k	1 in 20	1 in 2,000
European (Finnish)	~27k	1 in 81	1 in 920
Admixed American	~22k	1 in 20	1 in 410
African / African American	~21k	1 in 21	1 in 510
East Asian	~20k	1 in 29	1 in 340
Ashkenazi Jewish	~13k	1 in 86	≈ 1 in 2,700
Middle Eastern	~2,884	1 in 25	≈ 1 in 2,900

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): 13 of 26 coding exons well covered in gnomAD exomes; exons 3, 4, 6, 7, 9 and 8 more marginal. Genomes: all 26.? see exons ↓