GC

protein-coding

GC vitamin D binding protein

Gene summary

The protein encoded by this gene belongs to the albumin gene family. It is a multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid and on the surface of many cell types. It binds to vitamin D and its plasma metabolites and transports them to target tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

MANE transcript

NM_000583.4

Inheritance

—

ClinVar variants

U:53B:12

Top phenotype

Chronic obstructive pulmonary disease

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr4:71,741,696-71,804,041

External References & Databases

Ensembl (ENSG00000145321)

Transcript & Mutation Effects

hg38 • Region Span ~62.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GC variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 44

Chronic obstructive pulmonary diseaseTotal: 11

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000583.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar	4 clinvar	6
missense			45 clinvar	4 clinvar	2 clinvar	51
nonsense			1 clinvar			1
start loss						0
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	53	6	6	65

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000583.4	RefSeq	NP_000574.2	12	MANE Select
ENST00000273951.13	Ensembl	ENSP00000273951.8	12	MANE Select
NM_001204306.1	RefSeq	NP_001191235.1	12	Standard
NM_001204307.1	RefSeq	NP_001191236.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vitamin D Metabolism
Metabolism of lipids
Metabolism
Metabolism of steroids
Vitamin D (calciferol) metabolism

Biological Process

vitamin transmembrane transport
vitamin D metabolic process
vitamin transport

Molecular Function

actin binding
vitamin D binding
vitamin transmembrane transporter activity
calcidiol binding

Cellular Component

extracellular region
extracellular space
cytosol
lysosomal lumen
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000504199
Coding exons: 13
Length: 62349
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125745
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.399	231	249	0.929	0.0000118	3204
Missense (PolyPhen)		57	66.286	0.85991		865
Synonymous	-0.362	100	95.5	1.05	0.00000486	928
Loss of Function	1.22	20	26.8	0.746	0.00000131	365

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.00030	0.00029	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5 alpha for neutrophils in inflammation and macrophage activation. {ECO:0000305|PubMed:16302727}.;

Recessive Scores

pRec: 0.430

Intolerance Scores

LoFtool: 0.432
RVIS EVS: 0.04
RVIS percentile EVS: 57.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.815

Gene Damage Prediction

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