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 metal ion binding activity. Predicted to be involved in positive regulation of gene expression. Predicted to act upstream of or within response to bacterium. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.95

Clinical Summary— FER1L6

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

250 VUS of 306 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.5772th %ile

GOF

0.6443th %ile

LOF

0.48top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

306 submitted variants in ClinVar

ClinVar

Classification Summary

VUS250

Likely Benign19

Benign11

250

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	250	0	0	250
Likely Benign	13	1	5	19
Benign	4	1	6	11
Total	267	2	11	280

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

View in ClinVar →

50 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap FER1L6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →