GFER

growth factor, augmenter of liver regeneration

Basic information

Region (hg38): 16:1984192-1987749

Links

ENSG00000127554 ∙ NCBI:2671 ∙ OMIM:600924 ∙ HGNC:4236 ∙ Uniprot:P55789 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome (Limited), mode of inheritance: AR
• congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome (Supportive), mode of inheritance: AR
• congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Musculoskeletal; Neurologic; Ophthalmologic	19409522

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GFER gene.

• Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome (4 variants)
• not provided (3 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFER gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	38	2	41
missense	1	1	53	4	1	60
nonsense	2	1	1	1		5
start loss						0
frameshift	1	1	2			4
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				2	1	3
non coding				12	6	18
Total	4	3	58	55	9

Highest pathogenic variant AF is 0.0000722

Variants in GFER

This is a list of pathogenic ClinVar variants found in the GFER region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-1984224-G-C			Likely benign (Jul 23, 2022)
16-1984227-G-A			Likely benign (Nov 20, 2023)
16-1984230-C-T		not specified	Likely benign (Jul 10, 2023)
16-1984232-G-C		not specified	Conflicting classifications of pathogenicity (Feb 25, 2022)
16-1984236-G-C			Uncertain significance (Oct 13, 2022)
16-1984241-GC-G			Uncertain significance (Oct 31, 2016)
16-1984252-G-A		Inborn genetic diseases	Uncertain significance (Dec 02, 2022)
16-1984253-G-C			Uncertain significance (Apr 03, 2023)
16-1984254-C-T			Likely benign (Sep 24, 2022)
16-1984255-G-C			Uncertain significance (Sep 14, 2022)
16-1984259-A-C		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
16-1984260-C-G		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
16-1984260-C-T			Likely benign (Oct 05, 2023)
16-1984263-C-G			Likely benign (Sep 14, 2022)
16-1984269-C-T			Likely benign (Apr 09, 2022)
16-1984271-T-G			Uncertain significance (May 24, 2022)
16-1984273-C-T		not specified	Uncertain significance (Jun 28, 2023)
16-1984274-C-T			Uncertain significance (Nov 27, 2023)
16-1984275-G-C		not specified	Benign (Jan 26, 2024)
16-1984279-G-A		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
16-1984281-C-T			Uncertain significance (Jan 01, 2022)
16-1984286-G-C			Uncertain significance (Aug 08, 2022)
16-1984290-C-T			Likely benign (Sep 02, 2022)
16-1984308-G-A			Likely benign (Jun 24, 2022)
16-1984330-G-A			Uncertain significance (May 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFER	protein_coding	protein_coding	ENST00000248114	3	3543

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000173	0.471	125599	0	19	125618	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.195	114	108	1.05	0.00000598	1319
Missense in Polyphen		45	36.95	1.2179		455
Synonymous	-0.329	50	47.1	1.06	0.00000237	410
Loss of Function	0.304	6	6.86	0.875	2.97e-7	75

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000895	0.000894
East Asian	0.00	0.00
Finnish	0.0000466	0.0000462
European (Non-Finnish)	0.0000706	0.0000705
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: FAD-dependent sulfhydryl oxidase that regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re- oxidized by donating electrons to cytochrome c or molecular oxygen. {ECO:0000269|PubMed:19397338, ECO:0000269|PubMed:20593814, ECO:0000269|PubMed:21383138, ECO:0000269|PubMed:22224850, ECO:0000269|PubMed:23186364, ECO:0000269|PubMed:23676665}.
• Pathway: Metabolism of proteins;Mitochondrial protein import (Consensus)

Recessive Scores

• pRec: 0.304

Haploinsufficiency Scores

• pHI: 0.0720
• hipred: N
• hipred_score: 0.459
• ghis: 0.586

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.897

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gfer
• Phenotype: neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; immune system phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: gfer
• Affected structure: exocrine pancreas
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: regulation of signaling receptor activity;oxidation-reduction process
• Cellular component: extracellular region;mitochondrion;mitochondrial intermembrane space;cytosol
• Molecular function: protein binding;growth factor activity;protein disulfide oxidoreductase activity;flavin-linked sulfhydryl oxidase activity;flavin adenine dinucleotide binding