C18orf32

protein-coding

chromosome 18 open reading frame 32

Gene summary

Involved in positive regulation of canonical NF-kappaB signal transduction. Located in endoplasmic reticulum and lipid droplet. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001035005.4

Inheritance

ClinVar variants

U:3

Top phenotype

Glycosylphosphatidylinositol biosynthesis defect 25

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr18:49,477,243-49,487,252

External References & Databases

Ensembl (ENSG00000177576)

Transcript & Mutation Effects

hg38 • Region Span ~10.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

glycosylphosphatidylinositol biosynthesis defect 25LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859271

Submitter: Ambry Genetics

glycosylphosphatidylinositol biosynthesis defect 25LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0859271

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Glycosylphosphatidylinositol biosynthesis defect 25AR

Manifestation: Biochemical; Neurologic

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: 35107634

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to C18orf32 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 2

not providedTotal: 1

Glycosylphosphatidylinositol biosynthesis defect 25Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001035005.4. 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						0
missense			2 clinvar			2
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	3	0	0	3

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001035005.4	RefSeq	NP_001030177.1	2	MANE Select
ENST00000318240.8	Ensembl	ENSP00000323199.3	2	MANE Select
NM_001199346.2	RefSeq	NP_001186275.1	2	Standard
ENST00000582392.2	Ensembl	ENSP00000462538.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of I-kappaB kinase/NF-kappaB signaling

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318240
Coding exons: 2
Length: 5595
Individuals with no LoFs: 125649
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125655
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.129	40	42.4	0.944	0.00000216	499
Missense (PolyPhen)		5	10.616	0.47098		147
Synonymous	0.0497	13	13.2	0.983	6.31e-7	137
Loss of Function	0.989	1	2.78	0.360	1.17e-7	34

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May activate the NF-kappa-B signaling pathway. {ECO:0000269|PubMed:12761501}.;

Intolerance Scores

LoFtool: 0.486
RVIS EVS: 0.15
RVIS percentile EVS: 64.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low