SAMD7

protein-coding

sterile alpha motif domain containing 7, the group of Sterile alpha motif domain containing

Gene summary

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific; chromatin binding activity; and histone binding activity. Predicted to be involved in negative regulation of DNA-templated transcription; negative regulation of gene expression, epigenetic; and retinal rod cell development. Predicted to be located in cytoplasm. Predicted to be part of PRC1 complex. Predicted to be active in nucleus. Implicated in macular degeneration. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001304366.2

Inheritance

ClinVar variants

P:6U:61B:3

Top phenotype

Macular dystrophy with or without cone dysfunction

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr3:169,911,572-169,939,175

External References & Databases

Ensembl (ENSG00000187033)

Transcript & Mutation Effects

hg38 • Region Span ~27.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

macular dystrophy with or without cone dysfunctionSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0958326

Submitter: PanelApp Australia

macular dystrophy with or without cone dysfunctionMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0958326

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Macular dystrophy with or without cone dysfunctionAR

Manifestation: Ophthalmologic

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: 38272031

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SAMD7 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 61

Macular dystrophy with or without cone dysfunctionTotal: 4

MACULAR DYSTROPHY WITH CONE DYSFUNCTIONTotal: 3

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001304366.2. 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			1
missense	2 clinvar		58 clinvar	3 clinvar		63
nonsense	1 clinvar					1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)	3 clinvar		1 clinvar			4
Total	6	0	61	3	0	70

Highest pathogenic variant AF is 0.000008745288

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001304366.2	RefSeq	NP_001291295.1	7	MANE Select
ENST00000335556.7	Ensembl	ENSP00000334668.3	7	MANE Select
NM_182610.4	RefSeq	NP_872416.1	7	Standard
ENST00000428432.6	Ensembl	ENSP00000391299.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of gene expression

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000428432
Coding exons: 7
Length: 27604
Individuals with no LoFs: 125707
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125747
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.180	241	249	0.968	0.0000125	2922
Missense (PolyPhen)		45	44.084	1.0208		589
Synonymous	-0.0954	89	87.9	1.01	0.00000452	879
Loss of Function	1.39	12	18.4	0.651	9.79e-7	204

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.000069	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the regulation of gene expression in the retina. It functions as a negative regulator of CRX-controlled genes. {ECO:0000250|UniProtKB:Q8C8Y5}.;

Recessive Scores

pRec: 0.0873

Intolerance Scores

LoFtool: 0.719
RVIS EVS: 0.09
RVIS percentile EVS: 60.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0486

Gene Damage Prediction

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