NDC1

protein-coding

NDC1 transmembrane nucleoporin, the group of Nucleoporins

Gene summary

A structural constituent of nuclear pore. Involved in nuclear pore complex assembly and nuclear pore localization. Located in nuclear membrane. Part of nuclear pore. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

TMEM48

MANE transcript

NM_018087.5

Inheritance

ClinVar variants

U:107B:5

Top phenotype

triple-A syndrome

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr1:53,765,478-53,838,463

External References & Databases

Ensembl (ENSG00000058804)

Transcript & Mutation Effects

hg38 • Region Span ~73.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

triple-A syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009279

Submitter: PanelApp Australia

neurodevelopmental disorder with achalasia, polyneuropathy, and alacrimaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0979875

Submitter: G2P

polyneuropathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001824

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NDC1 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 92

Neurodevelopmental disorder with achalasia, polyneuropathy, and alacrimaTotal: 3

Hereditary coproporphyriaTotal: 3

not providedTotal: 1

Cleft palateTotal: 1

NDC1-related disorderTotal: 1

Retinal disorderTotal: 1

Global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018087.5. 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			2
missense			99 clinvar	5 clinvar		104
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	107	5	0	112

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018087.5	RefSeq	NP_060557.3	18	MANE Select
ENST00000371429.4	Ensembl	ENSP00000360483.3	18	MANE Select
NM_001168551.2	RefSeq	NP_001162023.1	18	Standard
ENST00000874541.1	Ensembl	ENSP00000544600.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
tRNA processing
Disease
Gene expression (Transcription)
Regulation of HSF1-mediated heat shock response

Biological Process

mRNA export from nucleus
nuclear pore organization
synapsis
spermatogenesis
protein transport

Molecular Function

structural constituent of nuclear pore

Cellular Component

nuclear envelope
nuclear pore
cytoplasm
plasma membrane
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371429
Coding exons: 18
Length: 73401
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125744
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.09	290	347	0.835	0.0000167	4366
Missense (PolyPhen)		88	122.79	0.7167		1680
Synonymous	-0.875	139	126	1.10	0.00000608	1309
Loss of Function	5.17	4	38.7	0.103	0.00000182	477

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	0.000094	0.000092	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.000075	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope. Required for NPC and nuclear envelope assembly, possibly by forming a link between the nuclear envelope membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane. {ECO:0000269|PubMed:16600873, ECO:0000269|PubMed:16702233}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

RVIS EVS: -0.09
RVIS percentile EVS: 46.99

Essentials

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

Gene Damage Prediction

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