GFER

Chr 16AR

growth factor, augmenter of liver regeneration

Also known as: ALR, ERV1, HERV1, HPO, HPO1, HPO2, HSS, MMCHD

NCBI Gene: 2671 ENSG00000127554 UniProt: P55789 OMIM: 600924

GFER encodes a FAD-dependent sulfhydryl oxidase that regenerates disulfide bonds in the mitochondrial chaperone CHCHD4/MIA40, which is essential for protein folding in the mitochondrial intermembrane space. Autosomal recessive mutations cause mitochondrial progressive myopathy with congenital cataract and developmental delay, affecting muscle, eye, and neurodevelopmental systems from early life.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The hepatotrophic factor designated augmenter of liver regeneration (ALR) is thought to be one of the factors responsible for the extraordinary regenerative capacity of mammalian liver. It has also been called hepatic regenerative stimulation substance (HSS). The gene resides on chromosome 16 in the interval containing the locus for polycystic kidney disease (PKD1). The putative gene product is 42% similar to the scERV1 protein of yeast. The yeast scERV1 gene had been found to be essential for oxidative phosphorylation, the maintenance of mitochondrial genomes, and the cell division cycle. The human gene is both the structural and functional homolog of the yeast scERV1 gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.651 OMIM phenotype

Clinical Summary— GFER

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

9 unique Pathogenic / Likely Pathogenic· 75 VUS of 185 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?

1.65LOEUF

pLI 0.000

Z-score 0.30

OE 0.87 (0.48–1.65)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.20Z-score

OE missense 1.05 (0.90–1.23)

114 obs / 108.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.87 (0.48–1.65)

0≤0.351.4

Missense OE?1.05 (0.90–1.23)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 6 / 6.9Missense obs/exp: 114 / 108.3Syn Z: -0.33

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateGFER-related mitochondrial progressive myopathy with congenital cataract, hearing loss and developmental delayLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6743th %ile

GOF

0.5857th %ile

LOF

0.3261th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

185 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic5

VUS75

Likely Benign75

Benign15

Conflicting9

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	0	0	4
Likely Pathogenic	2	2	1	0	5
VUS	4	70	1	0	75
Likely Benign	1	3	21	50	75
Benign	0	1	11	3	15
Conflicting	—				9
Total	9	78	34	53	183

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

View in ClinVar →

45 pathogenic / likely-pathogenic (of 62) ClinVar copy-number / structural variants overlap GFER — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →