SAMD12

Summary

SAMD12 (sterile alpha motif domain containing 12, HGNC:31750) is a protein-coding gene on chromosome 8q24.11-q24.12, encoding Sterile alpha motif domain-containing protein 12 (Q8N8I0).

Predicted to be involved in cell surface receptor protein tyrosine kinase signaling pathway. Predicted to be active in cytoplasmic side of plasma membrane. Implicated in familial adult myoclonic epilepsy 1.

Source: NCBI Gene 401474 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy, familial adult myoclonic, 1 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 42 total — 3 pathogenic
• Phenotypes (HPO): 19
• MANE Select transcript: NM_207506

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31750
Approved symbol	SAMD12
Name	sterile alpha motif domain containing 12
Location	8q24.11-q24.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ39458
Ensembl gene	ENSG00000177570
Ensembl biotype	protein_coding
OMIM	618073
Entrez	401474

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding_CDS_not_defined, 4 protein_coding, 1 nonsense_mediated_decay

ENST00000314727, ENST00000409003, ENST00000445741, ENST00000453675, ENST00000524796, ENST00000526328, ENST00000526765, ENST00000648422, ENST00000649198, ENST00000649630, ENST00000964565

RefSeq mRNA: 4 — MANE Select: NM_207506 NM_001101676, NM_001349811, NM_001363274, NM_207506

CCDS: CCDS47913, CCDS6325, CCDS94334

Canonical transcript exons

ENST00000314727 — 4 exons

Exon	Start	End
ENSE00001272965	118439832	118439961
ENSE00001272978	118580715	118580893
ENSE00001272996	118377984	118379700
ENSE00002146278	118621804	118621963

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 91.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5354 / max 695.0491, expressed in 1028 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94585	6.8733	989
94578	1.5157	350
94586	0.0881	23
94584	0.0583	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	91.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.82	gold quality
bone marrow cell	CL:0002092	83.70	gold quality
calcaneal tendon	UBERON:0003701	83.47	gold quality
islet of Langerhans	UBERON:0000006	83.43	gold quality
prefrontal cortex	UBERON:0000451	82.17	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.53	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.18	gold quality
right frontal lobe	UBERON:0002810	77.74	gold quality
rectum	UBERON:0001052	77.66	gold quality
anterior cingulate cortex	UBERON:0009835	77.49	gold quality
cortical plate	UBERON:0005343	77.03	gold quality
mucosa of transverse colon	UBERON:0004991	76.32	gold quality
cerebellar cortex	UBERON:0002129	75.82	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.82	gold quality
cerebellar hemisphere	UBERON:0002245	75.77	gold quality
stromal cell of endometrium	CL:0002255	75.71	gold quality
pancreas	UBERON:0001264	75.69	gold quality
spinal cord	UBERON:0002240	75.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.28	gold quality
right lung	UBERON:0002167	74.96	gold quality
left lobe of thyroid gland	UBERON:0001120	74.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.53	gold quality
adenohypophysis	UBERON:0002196	74.26	gold quality
gall bladder	UBERON:0002110	74.21	gold quality
thyroid gland	UBERON:0002046	74.11	gold quality
corpus callosum	UBERON:0002336	74.01	gold quality
neocortex	UBERON:0001950	73.94	gold quality
frontal cortex	UBERON:0001870	73.86	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.82
E-MTAB-6678	yes	5.29
E-GEOD-111727	no	2028.25
E-MTAB-6075	no	128.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting SAMD12, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-5580-3P	99.70	69.41	2052

Literature-anchored findings (GeneRIF, showing 10)

• Abnormal expansions of TTTCA and TTTTA repeats in intron 4 of SAMD12 cause benign adult familial myoclonic epilepsy. Single-molecule, real-time sequencing of BAC clones and nanopore sequencing of genomic DNA identified two repeat configurations in SAMD12. (PMID:29507423)
• We identified the pentanucleotide repeat expansion in SAMD12 as the causative mutation in Chinese FCMTE pedigrees. (PMID:30194086)
• LncRNA SAMD12-AS1 promotes cell proliferation and inhibits apoptosis by interacting with NPM1. (PMID:31406141)
• identified a novel expanded intronic (TTTGA)n insertion at the same site as the previously reported (TTTCA)n insertion in SAMD12 (PMID:31483537)
• LncRNA SAMD12-AS1 down-regulates P53 to promote malignant progression of glioma. (PMID:31646576)
• Familial adult myoclonic epilepsy type 1 SAMD12 TTTCA repeat expansion arose 17,000 years ago and is present in Sri Lankan and Indian families. (PMID:32203200)
• Founder effect of the TTTCA repeat insertions in SAMD12 causing BAFME1. (PMID:32973343)
• DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A. (PMID:33040085)
• Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and SAMD12 intronic repeat expansion. (PMID:33681653)
• Liver fibrosis-derived exosomal miR-106a-5p facilitates the malignancy by targeting SAMD12 and CADM2 in hepatocellular carcinoma. (PMID:37228062)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	SAMD12	ENSDARG00000115661
mus_musculus	Samd12	ENSMUSG00000058656
rattus_norvegicus	Samd12	ENSRNOG00000043390
drosophila_melanogaster	ave	FBGN0050476
caenorhabditis_elegans		WBGENE00044341

Paralogs (1): SAMD10 (ENSG00000130590)

Protein

Protein identifiers

Sterile alpha motif domain-containing protein 12 — Q8N8I0 (reviewed: Q8N8I0)

All UniProt accessions (4): B8ZZB7, Q8N8I0, F8VYB8, H0YEJ0

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in the brain.

Disease relevance. Epilepsy, familial adult myoclonic, 1 (FAME1) [MIM:601068] A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME1 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (4): NP_001095146, NP_001336740, NP_001350203, NP_997389* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR039144	Aveugle-like_SAM_dom	Domain
IPR052268	SAM_domain-containing_protein	Family

Pfam: PF07647

UniProt features (3 total): chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N8I0-F1	72.09	0.36

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 194 (showing top): AREB6_01, GGAMTNNNNNTCCY_UNKNOWN, NF1_Q6_01, BACH2_01, ZIC1_01, GOCC_CYTOPLASMIC_SIDE_OF_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, GOBP_CELL_SURFACE_RECEPTOR_PROTEIN_TYROSINE_KINASE_SIGNALING_PATHWAY, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, chr8q24, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_UP, GOBP_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY, ARNT2_TARGET_GENES, FOXN3_TARGET_GENES, MIR153_5P

GO Biological Process (2): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), biological_process (GO:0008150)

GO Molecular Function (2): molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasmic side of plasma membrane (GO:0009898), cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
enzyme-linked receptor protein signaling pathway	1
binding	1
plasma membrane	1
cytoplasmic side of membrane	1

Protein interactions and networks

STRING

572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAMD12	RAPGEF2	Q9Y4G8	758
SAMD12	STARD7	Q9NQZ5	758
SAMD12	MARCHF6	O60337	670
SAMD12	YEATS2	Q9ULM3	666
SAMD12	DAB1	O75553	573
SAMD12	TNRC6A	Q8NDV7	542
SAMD12	LRRC9	Q6ZRR7	529
SAMD12	ATN1	P54259	491
SAMD12	GCSAML	Q5JQS6	489
SAMD12	CACNA1A	P78510	445
SAMD12	CTNND2	Q9UQB3	424
SAMD12	UBXN10	Q96LJ8	415
SAMD12	ATXN10	Q9UBB4	409
SAMD12	EXT1	Q16394	404
SAMD12	SAMD13	Q5VXD3	403

IntAct

5 interactions, top by confidence:

A	B	Type	Score
USP20	SAMD12	psi-mi:“MI:0915”(physical association)	0.560
TPGS1	PIK3R2	psi-mi:“MI:0914”(association)	0.350
USP20	SAMD12	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): SAMD12 (Affinity Capture-RNA), SAMD12 (Two-hybrid), ANXA2 (Affinity Capture-RNA), HRNR (Affinity Capture-RNA), ARG1 (Affinity Capture-RNA), FLG (Affinity Capture-RNA), RPLP0 (Affinity Capture-RNA), FLNA (Affinity Capture-RNA), DCD (Affinity Capture-RNA), NPM1 (Affinity Capture-RNA), SAMD12 (Affinity Capture-RNA), SAMD12 (Affinity Capture-MS), SAMD12 (Two-hybrid)

ESM2 similar proteins: A4Q9F3, A6QPH9, O15444, P01344, P01346, P05017, P05019, P07455, P07456, P08025, P09535, P10763, P10764, P16501, P16545, P17085, P17647, P18254, P33712, P51457, P51458, P51459, P51462, Q02815, Q3U2E2, Q4R3D6, Q5EG05, Q5RDW3, Q5XI57, Q68LC0, Q6GUL6, Q6IVA5, Q6JLX1, Q80UW0, Q8C4U2, Q8K214, Q8N554, Q8N8I0, Q8R0A6, Q8TAG5

Diamond homologs: Q0VE29, Q5RDW3, Q7TST3, Q8ML92, Q8N8I0, Q9BYL1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	24
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
560216	SAMD12, 5-BP INS, TTTCA(n) REPEAT EXPANSION, IVS4	Pathogenic
800660	NC_000008.10:g.119379055_119379157TGAAA[100_?]TAAAA[40_?]	Pathogenic
872917	NC_000008.10:g.119379055_119379157TGAAA[149]TAAAA[446]	Pathogenic

SpliceAI

3003 predictions. Top by Δscore:

Variant	Effect	Δscore
8:118379557:TACC:T	donor_loss	1.0000
8:118379698:GCC:G	acceptor_gain	1.0000
8:118379699:CCC:C	acceptor_gain	1.0000
8:118379708:G:GC	acceptor_gain	1.0000
8:118379709:T:TC	acceptor_gain	1.0000
8:118379710:T:C	acceptor_gain	1.0000
8:118379710:T:TC	acceptor_gain	1.0000
8:118379711:T:C	acceptor_gain	1.0000
8:118379711:T:TC	acceptor_gain	1.0000
8:118580711:GCACC:G	donor_loss	1.0000
8:118580712:CA:C	donor_loss	1.0000
8:118580714:C:G	donor_loss	1.0000
8:118230472:T:TA	donor_gain	0.9900
8:118379572:A:C	donor_gain	0.9900
8:118379696:TCGCC:T	acceptor_gain	0.9900
8:118379697:CGCC:C	acceptor_gain	0.9900
8:118379697:CGCCC:C	acceptor_gain	0.9900
8:118379699:CC:C	acceptor_gain	0.9900
8:118379700:CC:C	acceptor_gain	0.9900
8:118379701:C:CC	acceptor_gain	0.9900
8:118379702:T:C	acceptor_loss	0.9900
8:118379704:C:CT	acceptor_gain	0.9900
8:118379708:G:C	acceptor_gain	0.9900
8:118379709:T:C	acceptor_gain	0.9900
8:118394286:T:A	donor_gain	0.9900
8:118439860:A:AC	donor_gain	0.9900
8:118439861:C:CC	donor_gain	0.9900
8:118439958:CTGA:C	acceptor_gain	0.9900
8:118439959:TGA:T	acceptor_gain	0.9900
8:118439962:C:CC	acceptor_gain	0.9900

AlphaMissense

1300 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:118379604:A:G	L140P	1.000
8:118379667:A:T	L119H	1.000
8:118379682:A:G	L114P	1.000
8:118439832:C:A	G108W	1.000
8:118439837:A:T	I106K	1.000
8:118439897:A:G	L86S	1.000
8:118439899:C:A	W85C	1.000
8:118439899:C:G	W85C	1.000
8:118439901:A:G	W85R	1.000
8:118439901:A:T	W85R	1.000
8:118439923:C:A	W77C	1.000
8:118439923:C:G	W77C	1.000
8:118439925:A:G	W77R	1.000
8:118439925:A:T	W77R	1.000
8:118379667:A:G	L119P	0.999
8:118379691:A:G	L111P	0.999
8:118379691:A:T	L111Q	0.999
8:118379700:C:A	G108V	0.999
8:118379700:C:T	G108E	0.999
8:118439832:C:G	G108R	0.999
8:118439832:C:T	G108R	0.999
8:118439837:A:C	I106R	0.999
8:118439837:A:G	I106T	0.999
8:118439852:A:G	F101S	0.999
8:118439900:C:G	W85S	0.999
8:118439909:A:T	V82D	0.999
8:118379577:A:G	L149P	0.998
8:118379610:A:G	L138P	0.998
8:118379656:C:A	G123W	0.998
8:118379661:C:G	R121P	0.998

dbSNP variants (sampled 300 via entrez): RS1000000142 (8:118409638 G>A), RS1000014615 (8:118232856 A>G), RS1000015658 (8:118367891 C>G), RS1000019838 (8:118462777 C>G,T), RS1000021608 (8:118535696 A>C,G), RS1000024004 (8:118283809 G>A), RS1000037971 (8:118365596 T>C,G), RS1000040247 (8:118424768 A>C), RS1000040725 (8:118239033 G>T), RS1000040941 (8:118614460 A>G), RS1000045753 (8:118192630 A>C), RS1000047053 (8:118603122 T>C), RS1000050198 (8:118233904 C>T), RS1000051787 (8:118320860 A>C), RS1000060290 (8:118410962 A>G)

Disease associations

OMIM: gene MIM:618073 | disease phenotypes: MIM:601068

GenCC curated gene-disease

Disease	Classification	Inheritance
epilepsy, familial adult myoclonic, 1	Strong	Autosomal dominant
benign adult familial myoclonic epilepsy	Supportive	Autosomal dominant

Mondo (2): epilepsy, familial adult myoclonic, 1 (MONDO:0010985), benign adult familial myoclonic epilepsy (MONDO:0019448)

Orphanet (1): Familial adult myoclonic epilepsy (Orphanet:86814)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001249	Intellectual disability
HP:0001312	Giant somatosensory evoked potentials
HP:0001326	EEG with irregular generalized spike and wave complexes
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001340	Enhancement of the C-reflex
HP:0001351	Jerk-locked premyoclonus spikes
HP:0002069	Bilateral tonic-clonic seizure
HP:0002123	Generalized myoclonic seizure
HP:0002197	Generalized-onset seizure
HP:0002315	Headache
HP:0002353	EEG abnormality
HP:0002378	Hand tremor
HP:0003581	Adult onset
HP:0003680	Nonprogressive
HP:0007359	Focal-onset seizure
HP:0010852	EEG with photoparoxysmal response
HP:0100576	Amaurosis fugax

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001860_8	Multiple sclerosis	8.000000e-06
GCST005212_12	Asthma	5.000000e-06
GCST006105_4	Eye morphology	3.000000e-07
GCST006620_13	Self-rated health	5.000000e-08
GCST007325_188	General risk tolerance (MTAG)	2.000000e-08
GCST010039_4	Adverse response to inhaled corticosteroid treatment x age interaction in asthma	4.000000e-07
GCST90002389_186	Lymphocyte percentage of white cells	2.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004778	self rated health
EFO:0008579	risk-taking behaviour
EFO:0008007	age at assessment
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563399	Epilepsy, Myoclonic, Benign Adult Familial, Type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	increases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
incobotulinumtoxinA	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Chromium	increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lead	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methylcholanthrene	affects binding, increases reaction	1
Nickel	decreases expression	1
Phthalic Acids	increases methylation	1
Progesterone	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C9HU	ZJUi013-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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