GRAMD1B

protein-coding

GRAM domain containing 1B, the group of GRAM domain containing

Gene summary

Enables cholesterol transfer activity. Involved in lysosome to ER cholesterol transport. Located in endoplasmic reticulum; endoplasmic reticulum-plasma membrane contact site; and plasma membrane. Is active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

LINC01059

MANE transcript

NM_001387025.1

Inheritance

ClinVar variants

P:1U:83B:13

Top phenotype

GRAMD1B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr11:123,358,428-123,627,774

External References & Databases

Ensembl (ENSG00000023171)

Transcript & Mutation Effects

hg38 • Region Span ~269.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: LiferaOmics

Genetic evidence – Published: PMID: 28097321 – Reports one consanguineous family with two affected females harboring a homozygous missense variant. Case-level (non-LOF missense in AR model) = 0.1; segregation (one additional affected sibling; conservative) = 0.5; case-control = 0; PMID: 28097321 total = 0.6 PMID: 30167849 – Reports one family with a homozygous stop gained variant in GRAMD1B; however, a second rare damaging variant in TBRG1 is present and authors state both variants may contribute to the phenotype; causality cannot be attributed solely to GRAMD1B. Case-level = 0; segregation = 0; case-control = 0; PMID: 30167849 total = 0 Published genetic evidence total = 0.6/12 Genetic evidence – Our cases: Family 1 –one proband (biallelic predicted null in AR model; homozygous scored once; −0.5 consanguinity deduction applied) = 1.0; segregation = 0; case-control = 0; Family 1 total = 1.0 Our cases total = 1.0/12 Total genetic evidence (published + our cases) = 1.6/12 Experimental evidence – Published: PMID: 30167849 – Reports differential expression of GRAMD1B in adult cerebellar cortex and basal nuclei during development; no neuronal functional studies, no in vivo neurodevelopmental model, and no rescue data linking GRAMD1B dysfunction to neurodevelopmental phenotype. Function consistent with disease = 0; functional alteration = 0; model systems = 0; rescue = 0; PMID: 30167849 experimental total = 0 Experimental evidence total = 0/6 Overall score = 1.6

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GRAMD1B variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 80

GRAMD1B-related disorderTotal: 10

not providedTotal: 7

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001387025.1. 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			1 clinvar	4 clinvar	1 clinvar	6
missense			78 clinvar	6 clinvar	2 clinvar	86
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	83	10	3	97

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 77 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001387025.1	RefSeq	NP_001373954.1	20	MANE Select
ENST00000635736.2	Ensembl	ENSP00000490062.1	20	MANE Select
NM_001286563.3	RefSeq	NP_001273492.1	21	Standard
NM_001286564.3	RefSeq	NP_001273493.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ectoderm Differentiation

Biological Process

cholesterol transport
cholesterol homeostasis
cellular response to cholesterol
intermembrane sterol transfer

Molecular Function

phosphatidylserine binding
cholesterol binding
phosphatidic acid binding
intermembrane cholesterol transfer activity

Cellular Component

endoplasmic reticulum membrane
plasma membrane
membrane
integral component of membrane
endoplasmic reticulum-plasma membrane contact site

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000529750
Coding exons: 20
Length: 102139
Individuals with no LoFs: 124629
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 124638
p: 0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.23	249	440	0.566	0.0000270	4838
Missense (PolyPhen)		60	149.89	0.4003		1584
Synonymous	-0.0143	176	176	1.00	0.0000120	1314
Loss of Function	5.37	5	43.0	0.116	0.00000217	488

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00013	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.353
RVIS EVS: -0.47
RVIS percentile EVS: 23.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.169

Gene Damage Prediction

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