GFER

Chr 16AR

growth factor, augmenter of liver regeneration

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

NCBI Gene: 2671ENSG00000127554UniProt: P55789

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]

Primary Disease Associations & Inheritance

Myopathy, mitochondrial progressive, with congenital cataract and developmental delayMIM #613076
AR
243
ClinVar variants
53
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GFER
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 91 VUS of 243 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.20Z-score
OE missense 1.05 (0.90–1.23)
114 obs / 108.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.87 (0.48–1.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.90–1.23)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 6 / 6.9Missense obs/exp: 114 / 108.3Syn Z: -0.33

ClinVar Variant Classifications

243 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic5
VUS91
Likely Benign75
Benign15
Conflicting9
48
Pathogenic
5
Likely Pathogenic
91
VUS
75
Likely Benign
15
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
45
0
48
Likely Pathogenic
1
1
3
0
5
VUS
3
70
18
0
91
Likely Benign
1
3
21
50
75
Benign
0
1
11
3
15
Conflicting
—9
Total6779853243

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

View in ClinVar →

Protein Context — Lollipop Plot

GFER · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GFER-related mitochondrial progressive myopathy with congenital cataract, hearing loss and developmental delay

moderate
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Myopathy, mitochondrial progressive, with congenital cataract and developmental delay

MIM #613076

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Adrenal Insufficiency in Mitochondrial Disease: A Rare Case of GFER-Related Mitochondrial Encephalomyopathy and Review of the Literature.
Calderwood L et al.·J Child Neurol
2016Review
Augmenter of liver regeneration: Essential for growth and beyond.
Ibrahim S et al.·Cytokine Growth Factor Rev
2019Review
Rapid Targeted Genomics in Critically Ill Newborns.
van Diemen CC et al.·Pediatrics
2017Clinical trial
Polymorphism rs1046495 of the GFER Gene as a New Genetic Marker of Preposition to Type 2 Diabetes Mellitus.
Klyosova EY et al.·Bull Exp Biol Med
2022
Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data.
Nambot S et al.·Clin Genet
2017
NFE2L2 is associated with NQO1 expression and low stage of hepatic fibrosis in patients with chronic hepatitis C.
Wójcik KM et al.·Adv Clin Exp Med
2019Cohort
Encephalomyopathies caused by abnormal nuclear-mitochondrial intergenomic cross-talk.
Lamperti C et al.·Acta Myol
2009
[Analysis of gene expression profiles among 3 epithelial ovarian tumor subtypes using cDNA and tissue microarrays].
Zheng M et al.·Ai Zheng
2004
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools