LDLRAD4

protein-coding

low density lipoprotein receptor class A domain containing 4, the group of MicroRNA protein coding host genes

Gene summary

Enables R-SMAD binding activity. Involved in negative regulation of cell migration; negative regulation of epithelial to mesenchymal transition; and negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway. Located in early endosome membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C18orf1

MANE transcript

NM_001378100.1

Inheritance

—

ClinVar variants

U:47B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr18:13,217,498-13,652,755

External References & Databases

Ensembl (ENSG00000168675)

Transcript & Mutation Effects

hg38 • Region Span ~435.3 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 LDLRAD4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001378100.1. 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						0
missense			46 clinvar	1 clinvar		47
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	47	1	0	48

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 135 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001378100.1	RefSeq	NP_001365029.1	5	MANE Select
ENST00000359446.11	Ensembl	ENSP00000352420.5	5	MANE Select
NM_001003674.3	RefSeq	NP_001003674.1	4	Standard
NM_001003675.3	RefSeq	NP_001003675.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of epithelial to mesenchymal transition
negative regulation of SMAD protein complex assembly
negative regulation of cell migration
negative regulation of transforming growth factor beta receptor signaling pathway
negative regulation of pathway-restricted SMAD protein phosphorylation

Molecular Function

R-SMAD binding

Cellular Component

nucleoplasm
integral component of membrane
early endosome membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361205
Coding exons: 5
Length: 435258
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125747
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.57	137	200	0.686	0.0000128	2019
Missense (PolyPhen)		44	83.369	0.52778		846
Synonymous	-0.189	88	85.8	1.03	0.00000631	603
Loss of Function	2.63	2	11.7	0.171	6.71e-7	120

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)	0.000026	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal. {ECO:0000269|PubMed:24627487}.;

Recessive Scores

pRec: 0.0990

Intolerance Scores

RVIS EVS: -0.12
RVIS percentile EVS: 45.13

Essentials

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

Gene Damage Prediction

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