SAMD7

Summary

SAMD7 (sterile alpha motif domain containing 7, HGNC:25394) is a protein-coding gene on chromosome 3q26.2, encoding Sterile alpha motif domain-containing protein 7 (Q7Z3H4). Component of a Polycomb group (PcG) multiprotein PRC1-like complex, essential for establishing rod photoreceptor cell identity and function by silencing nonrod gene expression in developing rod photoreceptor cells.

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.

Source: NCBI Gene 344658 — RefSeq curated summary.

At a glance

• Gene–disease (curated): macular dystrophy with or without cone dysfunction (Strong, GenCC)
• Clinical variants (ClinVar): 68 total — 5 pathogenic
• Phenotypes (HPO): 11
• MANE Select transcript: NM_001304366

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25394
Approved symbol	SAMD7
Name	sterile alpha motif domain containing 7
Location	3q26.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686E1583
Ensembl gene	ENSG00000187033
Ensembl biotype	protein_coding
OMIM	620493
Entrez	344658

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000335556, ENST00000428432, ENST00000487910

RefSeq mRNA: 2 — MANE Select: NM_001304366 NM_001304366, NM_182610

CCDS: CCDS3209

Canonical transcript exons

ENST00000335556 — 9 exons

Exon	Start	End
ENSE00001333464	169925058	169925136
ENSE00001333466	169921214	169921338
ENSE00001333470	169938318	169939175
ENSE00001333471	169919458	169919584
ENSE00001345467	169915367	169915441
ENSE00001345474	169911572	169911821
ENSE00003560424	169928457	169928578
ENSE00003571431	169926553	169927181
ENSE00003628905	169936339	169936449

Expression profiles

Bgee: expression breadth tissue_specific, 3 present calls, max score 40.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0430 / max 38.0700, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39679	0.0259	4
39680	0.0171	3

Top tissues by expression

125 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	40.36	gold quality
lymph node	UBERON:0000029	40.24	gold quality
cortical plate	UBERON:0005343	40.04	gold quality
bone marrow cell	CL:0002092	38.26	gold quality
ganglionic eminence	UBERON:0004023	37.26	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
bone marrow	UBERON:0002371	36.53	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
tonsil	UBERON:0002372	35.63	silver quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
monocyte	CL:0000576	30.88	gold quality
prefrontal cortex	UBERON:0000451	30.81	gold quality
leukocyte	CL:0000738	30.58	gold quality
blood	UBERON:0000178	30.22	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.51	gold quality
right uterine tube	UBERON:0001302	28.76	gold quality
duodenum	UBERON:0002114	28.14	gold quality
urinary bladder	UBERON:0001255	27.89	gold quality
frontal cortex	UBERON:0001870	27.52	gold quality
primary visual cortex	UBERON:0002436	27.50	gold quality
superior frontal gyrus	UBERON:0002661	26.98	gold quality
adrenal tissue	UBERON:0018303	26.96	gold quality
islet of Langerhans	UBERON:0000006	26.88	gold quality
cortex of kidney	UBERON:0001225	26.87	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	30.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CRX

miRNA regulators (miRDB)

28 targeting SAMD7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-4712-5P	97.24	67.79	775
HSA-MIR-770-5P	97.24	68.10	758
HSA-MIR-6772-3P	97.04	65.89	784
HSA-MIR-6823-5P	96.26	65.69	919

Literature-anchored findings (GeneRIF, showing 3)

• Data have identified a novel retinal SAM domain protein, Samd7, which could act as a transcriptional repressor involved in fine-tuning of Crx-regulated gene expression. (PMID:23565263)
• Autosomal recessive retinitis pigmentosa with homozygous rhodopsin mutation E150K and non-coding cis-regulatory variants in CRX-binding regions of SAMD7. (PMID:26887858)
• Mutations in SAMD7 cause autosomal-recessive macular dystrophy with or without cone dysfunction. (PMID:38272031)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	samd7	ENSDARG00000060354
mus_musculus	Samd7	ENSMUSG00000051860
rattus_norvegicus	Samd7	ENSRNOG00000027995
drosophila_melanogaster	l(3)mbt	FBGN0002441
drosophila_melanogaster	Sfmbt	FBGN0032475
caenorhabditis_elegans	lin-61	WBGENE00003041
caenorhabditis_elegans	mbtr-1	WBGENE00021661

Paralogs (18): SCMH1 (ENSG00000010803), MBTD1 (ENSG00000011258), SCML1 (ENSG00000047634), L3MBTL2 (ENSG00000100395), SCML2 (ENSG00000102098), PHC1 (ENSG00000111752), THAP10 (ENSG00000129028), PHC2 (ENSG00000134686), SAMD1 (ENSG00000141858), SCML4 (ENSG00000146285), L3MBTL4 (ENSG00000154655), SFMBT1 (ENSG00000163935), PHC3 (ENSG00000173889), L3MBTL1 (ENSG00000185513), SAMD11 (ENSG00000187634), SFMBT2 (ENSG00000198879), L3MBTL3 (ENSG00000198945), SAMD13 (ENSG00000203943)

Protein

Protein identifiers

Sterile alpha motif domain-containing protein 7 — Q7Z3H4 (reviewed: Q7Z3H4)

All UniProt accessions (2): F8WDF1, Q7Z3H4

UniProt curated annotations — full annotation on UniProt →

Function. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, essential for establishing rod photoreceptor cell identity and function by silencing nonrod gene expression in developing rod photoreceptor cells. Via its association with the PRC1-like complex, promotes epigenetic repressive marks H3K27me3 and H2AK119ub marks in nonrod genes, silencing their transcription. Represses Crx-controlled photoreceptor-specific gene expression.

Subunit / interactions. Monomer, homodimer and homooligomer. Component of a Polycomb group (PcG) multiprotein PRC1-like complex. Interacts with PHC2, NR2E3 and SAMD11. Interacts with RNF1 in a PHC2-dependent manner.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in the retina (at protein level). Expressed in the retinal inner and outer nuclear layers.

Disease relevance. Macular dystrophy with or without cone dysfunction (MDCD) [MIM:620762] A form of macular dystrophy, a retinal disease in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea. MDCD is a progressive, autosomal recessive form characterized by reduced visual acuity and macular atrophy involving the fovea. Some patients also exhibit mild generalized cone dysfunction. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The SAM domain mediates its oligomerization and localization to nuclear polycomb bodies.

RefSeq proteins (2): NP_001291295, NP_872416 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR050548	PcG_chromatin_remod_factors	Family

Pfam: PF00536

UniProt features (9 total): region of interest 3, sequence variant 3, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z3H4-F1	56.48	0.22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): AREB6_01, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, chr3q26, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EYE_PHOTORECEPTOR_CELL_DIFFERENTIATION, TGCTGAY_UNKNOWN, WTGAAAT_UNKNOWN, GOBP_PHOTORECEPTOR_CELL_DEVELOPMENT, GOBP_CAMERA_TYPE_EYE_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOBP_PHOTORECEPTOR_CELL_DIFFERENTIATION, GOCC_NUCLEAR_UBIQUITIN_LIGASE_COMPLEX, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_SENSORY_ORGAN_MORPHOGENESIS

GO Biological Process (5): negative regulation of gene expression, epigenetic (GO:0045814), negative regulation of DNA-templated transcription (GO:0045892), retinal rod cell development (GO:0046548), negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of gene expression (GO:0010629)

GO Molecular Function (4): DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), chromatin binding (GO:0003682), histone binding (GO:0042393), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), PRC1 complex (GO:0035102)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
eye photoreceptor cell development	1
retinal rod cell differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of transcription by RNA polymerase II	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
protein binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
nuclear ubiquitin ligase complex	1
PcG protein complex	1

Protein interactions and networks

STRING

352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAMD7	NR2E3	Q9Y5X4	649
SAMD7	SMAD7	O15105	596
SAMD7	GPR160	Q9UJ42	530
SAMD7	SAMD14	Q8IZD0	527
SAMD7	LRIT1	Q9P2V4	489
SAMD7	OPN1SW	P03999	474
SAMD7	OTOS	Q8NHW6	471
SAMD7	SAMD10	Q9BYL1	410
SAMD7	COPS9	Q8WXC6	396
SAMD7	CRX	O43186	392
SAMD7	SAMD5	Q5TGI4	387
SAMD7	SEC62	Q99442	386
SAMD7	PCBP4	P57723	364
SAMD7	SAMD1	Q6SPF0	361
SAMD7	ATP1A1	P05023	353

IntAct

32 interactions, top by confidence:

A	B	Type	Score
KRTAP6-3	SAMD7	psi-mi:“MI:0915”(physical association)	0.560
SAMD7	KRTAP3-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	SAMD7	psi-mi:“MI:0915”(physical association)	0.560
OIP5	SAMD7	psi-mi:“MI:0915”(physical association)	0.560
FAM168B	SAMD7	psi-mi:“MI:0915”(physical association)	0.560
SAMD7	TSC1	psi-mi:“MI:0915”(physical association)	0.560
SAMD7	WFS1	psi-mi:“MI:0915”(physical association)	0.560
SAMD7	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
SAMD7	RNF11	psi-mi:“MI:0915”(physical association)	0.560
SAMD7	GAPDHS	psi-mi:“MI:0914”(association)	0.530
SAMD7	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
SAMD7	KRTAP3-1	psi-mi:“MI:0915”(physical association)	0.000
SAMD7	FAM168B	psi-mi:“MI:0915”(physical association)	0.000
SAMD7	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
SAMD7	OIP5	psi-mi:“MI:0915”(physical association)	0.000
SAMD7	TSC1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): GAPDHS (Affinity Capture-MS), SON (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), SAMD11 (Affinity Capture-MS), SAMD7 (Synthetic Growth Defect), SAMD11 (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), FBP1 (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), SAMD7 (Synthetic Lethality), SAMD7 (Two-hybrid), SAMD7 (Two-hybrid), SAMD7 (Two-hybrid), SAMD7 (Two-hybrid), KRTAP3-1 (Two-hybrid)

ESM2 similar proteins: A0A1W2PPF3, A1YFX5, A5WWA0, A6NFE2, B0S6S9, D2HQI1, D3Z987, F1M5M3, F1MJR8, G3X9P6, O15016, O35892, P70347, Q14DL0, Q1X8D7, Q32L17, Q3UPF5, Q3V0M2, Q4KL20, Q52KR3, Q5DTZ0, Q5IR70, Q5XIP4, Q5Z8V7, Q66H65, Q68FV5, Q6TXF5, Q7M6U3, Q7XWS7, Q7Z3H4, Q86UW6, Q86XD8, Q8C5U9, Q8CCC3, Q8CEE6, Q8IV76, Q8IWB6, Q8IYU4, Q8IYW4, Q8K0B3

Diamond homologs: A2A5N8, B1B1A0, D3YUG0, D3YXK1, D3ZWK4, E1C2V1, O02274, O60284, O95251, P39769, P59178, P70047, P70475, P78364, P97500, Q01538, Q05BQ5, Q1JQD9, Q1RNF8, Q29L50, Q32N90, Q3MIF2, Q4V7W5, Q5DTW2, Q5R737, Q5SVQ0, Q5VUG0, Q5VXD3, Q64028, Q6DIN3, Q6P5G3, Q6SPE9, Q6SPF0, Q7Z3H4, Q80TY4, Q810T5, Q8BLB7, Q8C8Y5, Q8CFC2, Q8CHP6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

68 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	58
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3062149	NM_001304366.2(SAMD7):c.290+1G>A	Pathogenic
3062150	NM_001304366.2(SAMD7):c.919+1G>A	Pathogenic
3062151	NM_001304366.2(SAMD7):c.211+1G>A	Pathogenic
3062152	NM_001304366.2(SAMD7):c.1153G>A (p.Val385Ile)	Pathogenic
3062153	NM_001304366.2(SAMD7):c.992A>T (p.Asp331Val)	Pathogenic

SpliceAI

1187 predictions. Top by Δscore:

Variant	Effect	Δscore
3:169911818:GGAT:G	donor_gain	1.0000
3:169911819:G:GT	donor_gain	1.0000
3:169911819:GAT:G	donor_gain	1.0000
3:169911822:G:GG	donor_gain	1.0000
3:169911826:G:GG	donor_gain	1.0000
3:169927180:AGG:A	donor_loss	1.0000
3:169927183:T:G	donor_loss	1.0000
3:169928453:AAAG:A	acceptor_gain	1.0000
3:169911817:AGGAT:A	donor_gain	0.9900
3:169911818:GGATG:G	donor_gain	0.9900
3:169911820:AT:A	donor_gain	0.9900
3:169911822:G:A	donor_loss	0.9900
3:169911823:T:A	donor_loss	0.9900
3:169921213:GAGAT:G	acceptor_gain	0.9900
3:169925133:CCAGG:C	donor_loss	0.9900
3:169925134:CAGG:C	donor_loss	0.9900
3:169925135:AGGTA:A	donor_loss	0.9900
3:169925136:GG:G	donor_loss	0.9900
3:169925138:T:A	donor_loss	0.9900
3:169928448:A:AG	acceptor_gain	0.9900
3:169928449:T:G	acceptor_gain	0.9900
3:169928451:TTAAA:T	acceptor_loss	0.9900
3:169928452:TAAA:T	acceptor_loss	0.9900
3:169928453:A:AG	acceptor_gain	0.9900
3:169928454:A:G	acceptor_gain	0.9900
3:169928454:AAGG:A	acceptor_loss	0.9900
3:169928455:A:AT	acceptor_loss	0.9900
3:169928455:A:G	acceptor_gain	0.9900
3:169928589:GTT:G	donor_gain	0.9900
3:169928590:TTT:T	donor_gain	0.9900

AlphaMissense

2936 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:169936343:T:C	F349S	0.998
3:169928516:T:A	W327R	0.997
3:169928516:T:C	W327R	0.997
3:169936358:T:A	I354N	0.997
3:169936373:T:C	L359S	0.997
3:169936415:T:C	L373S	0.997
3:169936342:T:C	F349L	0.996
3:169936344:T:A	F349L	0.996
3:169936344:T:G	F349L	0.996
3:169936397:T:C	L367P	0.996
3:169936364:G:T	G356V	0.995
3:169936382:T:A	L362H	0.995
3:169936364:G:A	G356E	0.994
3:169936382:T:C	L362P	0.994
3:169936433:T:C	L379P	0.994
3:169936439:T:C	I381T	0.994
3:169928518:G:C	W327C	0.992
3:169928518:G:T	W327C	0.992
3:169928540:T:C	F335L	0.992
3:169928542:C:A	F335L	0.992
3:169928542:C:G	F335L	0.992
3:169928541:T:C	F335S	0.991
3:169936358:T:G	I354S	0.991
3:169936397:T:A	L367H	0.991
3:169936439:T:G	I381S	0.991
3:169936343:T:G	F349C	0.990
3:169936437:A:C	K380N	0.989
3:169936437:A:T	K380N	0.989
3:169928561:T:C	C342R	0.987
3:169936423:G:A	G376R	0.986

dbSNP variants (sampled 300 via entrez): RS1000096728 (3:169915429 G>A), RS1000147407 (3:169915697 G>C), RS1000210595 (3:169920392 T>A), RS1000242824 (3:169929599 T>C), RS1000526160 (3:169928207 A>C), RS1000578494 (3:169927955 A>G), RS1001043124 (3:169910775 A>T), RS1001154741 (3:169927475 T>C), RS1001196414 (3:169931617 G>A,C), RS1001211429 (3:169921741 A>T), RS1001247203 (3:169931355 T>C), RS1001458351 (3:169934024 G>A), RS1001478806 (3:169909573 G>C,T), RS1001662627 (3:169921998 A>G,T), RS1001740430 (3:169937700 A>C,G)

Disease associations

OMIM: gene MIM:620493 | disease phenotypes: MIM:620762

GenCC curated gene-disease

Disease	Classification	Inheritance
macular dystrophy with or without cone dysfunction	Strong	Autosomal recessive

Mondo (1): macular dystrophy with or without cone dysfunction (MONDO:0958326)

Orphanet (0):

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000603	Central scotoma
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0007401	Macular atrophy
HP:0007663	Reduced visual acuity
HP:0007722	Retinal pigment epithelial atrophy
HP:0007754	Macular dystrophy
HP:0011462	Young adult onset
HP:0012511	Temporal optic disc pallor
HP:0025159	Hypoautofluorescent retinal lesion

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases expression	1
Aflatoxin B1	decreases methylation	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.