FER1L6

Chr 8

fer-1 like family member 6

Also known as: C8ORFK23

NCBI Gene: 654463 ENSG00000214814 UniProt: Q2WGJ9 OMIM: 620884

FER1L6 encodes a calcium/phospholipid-binding protein essential for proper development of skeletal and cardiac muscle. Mutations cause autosomal recessive muscular dystrophy with cardiomyopathy, typically presenting in infancy or early childhood. The gene is not highly constrained, consistent with its recessive inheritance pattern affecting muscle and cardiac function.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable calcium-dependent phospholipid binding activity. Predicted to be involved in cardiac muscle tissue development; positive regulation of gene expression; and skeletal muscle tissue development. Predicted to act upstream of or within response to bacterium. Located in plasma membrane; recycling endosome; and trans-Golgi network. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.95

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.94

OE 0.79 (0.66–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.72Z-score

OE missense 0.94 (0.89–0.99)

942 obs / 1006.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.66–0.95)

0≤0.351.4

Missense OE?0.94 (0.89–0.99)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 77 / 97.7Missense obs/exp: 942 / 1006.7Syn Z: 1.63

Background carrier burden — how many people carry a rare variant somewhere in FER1L6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 22

2,322 rare PASS variants

Rare truncating (LoF)

1 in 170

421 rare PASS variants

Rare synonymous (reference)

1 in 47

829 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FER1L6. 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 34	1 in 250
South Asian	~43k	1 in 19	1 in 130
Remaining (unassigned)	~30k	1 in 20	1 in 150
European (Finnish)	~27k	1 in 81	1 in 720
Admixed American	~22k	1 in 19	1 in 140
African / African American	~21k	1 in 19	1 in 190
East Asian	~20k	1 in 21	1 in 140
Ashkenazi Jewish	~13k	1 in 110	1 in 1,100
Middle Eastern	~2,884	1 in 20	1 in 120

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): 39 of 40 coding exons well covered in gnomAD exomes; exon 37 marginal. Genomes: all 40.? see exons ↓