GeneBe

HBG1

protein-coding

hemoglobin subunit gamma 1, the group of Hemoglobin subunits

Gene summary

The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'-epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000559.3

Inheritance

AD, AR

ClinVar variants

U:30B:8

Top phenotype

Hereditary persistence of fetal hemoglobin

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr11:5,248,269-5,249,857

External References & Databases

Ensembl (ENSG00000213934)NCBI Gene (3047)OMIM (142200)HGNC:4831GenCCUniProt (P69891)AlphaFoldClinVar (HBG1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~1.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary persistence of fetal hemoglobin-beta-thalassemia syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0018749

Submitter: PanelApp Australia

hereditary persistence of fetal hemoglobin-sickle cell disease syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016672

Submitter: Orphanet

hereditary persistence of fetal hemoglobin-beta-thalassemia syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018749

Submitter: Orphanet

delta-beta-thalassemiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016489

Submitter: Orphanet

Clinical Genomic Database (CGD)

Hereditary persistence of fetal hemoglobinAD

Manifestation: Hematologic

Intervention: General

Rationale: 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

Refs: 2578620; 2423160; 21057501Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HBG1 variants in ClinVar

30 Conditions Cataloged
Hereditary persistence of fetal hemoglobinTotal: 8
not specifiedTotal: 8
Fetal hemoglobin quantitative trait locus 1Total: 2
not providedTotal: 1
HEMOGLOBIN F (JIANGSU)Total: 1
HEMOGLOBIN F (VICTORIA JUBILEE)Total: 1
HEMOGLOBIN F (KOTOBUKI)Total: 1
HEMOGLOBIN F (BASKENT)Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000559.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
0
missense
30
clinvar
7
clinvar
1
clinvar
 38
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total00307138
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000559.3RefSeqNP_000550.23MANE Select
ENST00000330597.5EnsemblENSP00000327431.43MANE Select
ENST00000632727.1EnsemblENSP00000488759.12Standard
ENST00000632727.2EnsemblENSP00000488759.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • ATF-2 transcription factor network

Biological Process

  • blood coagulation
  • oxygen transport
  • hydrogen peroxide catabolic process
  • protein heterooligomerization
  • cellular oxidant detoxification

Molecular Function

  • peroxidase activity
  • oxygen carrier activity
  • protein binding
  • oxygen binding
  • heme binding

Cellular Component

  • cytosol
  • hemoglobin complex
  • haptoglobin-hemoglobin complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000330597
Coding exons
3
Length
1810
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.7804056.50.7080.00000258948
Missense (PolyPhen)916.4470.54721314
Synonymous2.101124.10.4560.00000119291
Loss of Function1.4802.550.001.08e-749

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.;

Recessive Scores

pRec
0.783

Essentials

Essential (CRISPR)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.387

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumLowMedium
Primary ImmunodeficiencyMediumLowMedium
CancerMediumMediumMedium
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