SCML1

Summary

SCML1 (Scm polycomb group protein like 1, HGNC:10580) is a protein-coding gene on chromosome Xp22.13, encoding Sex comb on midleg-like protein 1 (Q9UN30). Putative Polycomb group (PcG) protein.

Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of DNA-templated transcription. Predicted to be located in female germ cell nucleus and male germ cell nucleus. Predicted to be active in nucleus.

Source: NCBI Gene 6322 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 45 total — 1 pathogenic
• MANE Select transcript: NM_001037540

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10580
Approved symbol	SCML1
Name	Scm polycomb group protein like 1
Location	Xp22.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000047634
Ensembl biotype	protein_coding
OMIM	300227
Entrez	6322

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 retained_intron

ENST00000380041, ENST00000380043, ENST00000380045, ENST00000398080, ENST00000419185, ENST00000427362, ENST00000487842, ENST00000895837, ENST00000895838, ENST00000895839, ENST00000895840, ENST00000918259, ENST00000918260

RefSeq mRNA: 4 — MANE Select: NM_001037540 NM_001037535, NM_001037536, NM_001037540, NM_006746

CCDS: CCDS14182, CCDS35210, CCDS35211

Canonical transcript exons

ENST00000380041 — 8 exons

Exon	Start	End
ENSE00002272658	17744071	17744219
ENSE00003532306	17753258	17754985
ENSE00003552461	17749400	17749504
ENSE00003608944	17746018	17746098
ENSE00003636742	17749894	17750293
ENSE00003670480	17745456	17745539
ENSE00003687638	17751815	17751966
ENSE00003841486	17737493	17737680

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 96.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.4092 / max 130.8094, expressed in 1609 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195674	4.4785	1352
195675	3.6972	1304
195676	3.0691	1101
195673	0.1264	39
195677	0.0380	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.61	gold quality
oocyte	CL:0000023	95.38	gold quality
left ovary	UBERON:0002119	92.69	gold quality
adrenal tissue	UBERON:0018303	91.90	gold quality
right testis	UBERON:0004534	91.55	gold quality
right ovary	UBERON:0002118	91.25	gold quality
left testis	UBERON:0004533	90.84	gold quality
testis	UBERON:0000473	90.44	gold quality
ovary	UBERON:0000992	90.43	gold quality
right lobe of liver	UBERON:0001114	90.26	gold quality
sperm	CL:0000019	89.68	gold quality
male germ cell	CL:0000015	89.20	gold quality
biceps brachii	UBERON:0001507	89.18	gold quality
liver	UBERON:0002107	88.98	gold quality
gastrocnemius	UBERON:0001388	88.29	gold quality
mucosa of stomach	UBERON:0001199	88.23	gold quality
endocervix	UBERON:0000458	87.75	gold quality
right adrenal gland cortex	UBERON:0035827	87.73	gold quality
tibial nerve	UBERON:0001323	87.65	gold quality
muscle of leg	UBERON:0001383	87.45	gold quality
right lung	UBERON:0002167	87.19	gold quality
left uterine tube	UBERON:0001303	87.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.91	gold quality
pigmented layer of retina	UBERON:0001782	86.77	gold quality
muscle organ	UBERON:0001630	86.70	gold quality
seminal vesicle	UBERON:0000998	86.67	gold quality
triceps brachii	UBERON:0001509	86.66	silver quality
subcutaneous adipose tissue	UBERON:0002190	86.60	gold quality
left adrenal gland cortex	UBERON:0035825	86.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	141.69
E-ANND-3	yes	7.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

128 targeting SCML1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 2)

• the molecular evolutionary pattern of SCML1 in diverse primate species showed a strong signature of adaptive evolution which is caused by Darwinian positive selection (PMID:18601738)
• Here, we report a microdeletion of 170,6 Kb at Xp22.13 (17.733.948-17.904.576) (GRCh37/hg19).The microdeletion harbors the NHS, SCLML1, and RAI2 genes and results in a phenotype consistent with Nance-Horan syndromesyndrome and developmental delay (PMID:28464487)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	phc1	ENSDARG00000002971
drosophila_melanogaster	l(3)mbt	FBGN0002441
drosophila_melanogaster	Scm	FBGN0003334
drosophila_melanogaster	Sfmbt	FBGN0032475
caenorhabditis_elegans	lin-61	WBGENE00003041
caenorhabditis_elegans	mbtr-1	WBGENE00021661

Paralogs (18): SCMH1 (ENSG00000010803), MBTD1 (ENSG00000011258), L3MBTL2 (ENSG00000100395), SCML2 (ENSG00000102098), PHC1 (ENSG00000111752), THAP10 (ENSG00000129028), PHC2 (ENSG00000134686), SAMD1 (ENSG00000141858), SCML4 (ENSG00000146285), L3MBTL4 (ENSG00000154655), SFMBT1 (ENSG00000163935), PHC3 (ENSG00000173889), L3MBTL1 (ENSG00000185513), SAMD7 (ENSG00000187033), SAMD11 (ENSG00000187634), SFMBT2 (ENSG00000198879), L3MBTL3 (ENSG00000198945), SAMD13 (ENSG00000203943)

Protein

Protein identifiers

Sex comb on midleg-like protein 1 — Q9UN30 (reviewed: Q9UN30)

All UniProt accessions (2): Q9UN30, Q5H966

UniProt curated annotations — full annotation on UniProt →

Function. Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. May be involved in spermatogenesis during sexual maturation.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Expressed in fetal and adult tissues.

Similarity. Belongs to the SCM family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UN30-3	3	yes
Q9UN30-1	1
Q9UN30-2	2

RefSeq proteins (4): NP_001032624, NP_001032625, NP_001032629, NP_006737 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR047531	SAM_Scm-like	Domain

Pfam: PF00536

UniProt features (7 total): modified residue 2, splice variant 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UN30-F1	67.08	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 138, 238

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 183 (showing top): BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, HNF3ALPHA_Q6, FOXO1_01, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, NKX62_Q2, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, FOXJ2_01, HP1SITEFACTOR_Q6, HFH3_01, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, LEE_EARLY_T_LYMPHOCYTE_DN, SCHLOSSER_SERUM_RESPONSE_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP

GO Biological Process (1): negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (3): chromatin binding (GO:0003682), histone binding (GO:0042393), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
protein binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

519 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCML1	ZNF394	Q53GI3	402
SCML1	NOL10	Q9BSC4	365
SCML1	GSAP	A4D1B5	334
SCML1	FLRT1	Q9NZU1	311
SCML1	WDR41	Q9HAD4	310
SCML1	APOLD1	Q96LR9	301
SCML1	ACOT13	Q9NPJ3	300
SCML1	PDZRN3	Q9UPQ7	300
SCML1	SNTB2	Q13425	297
SCML1	ADIRF	Q15847	290
SCML1	DBP	Q10586	287
SCML1	TFAP4	Q01664	283
SCML1	ESYT1	Q9BSJ8	275
SCML1	HLF	Q16534	271
SCML1	GPR6	P46095	271

IntAct

38 interactions, top by confidence:

A	B	Type	Score
CBX8	BMI1	psi-mi:“MI:0914”(association)	0.970
BMI1	CBX4	psi-mi:“MI:0914”(association)	0.900
PTPN3	YWHAQ	psi-mi:“MI:2364”(proximity)	0.850
PHC1	CBX4	psi-mi:“MI:0914”(association)	0.790
PTPN3	MCC	psi-mi:“MI:0914”(association)	0.660
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
CCDC43	PNKP	psi-mi:“MI:0914”(association)	0.640
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
SCML1	ARVCF	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
RNPS1	CASC3	psi-mi:“MI:0914”(association)	0.530
CBX6	RPS3	psi-mi:“MI:0914”(association)	0.530
SCML1	POTEKP	psi-mi:“MI:0915”(physical association)	0.400
PTPN4	TPR	psi-mi:“MI:0914”(association)	0.350
NPM3	KPNA3	psi-mi:“MI:0914”(association)	0.350
PSKH1	AIP	psi-mi:“MI:0914”(association)	0.350
AURKB	TARS3	psi-mi:“MI:0914”(association)	0.350
NPM1	RPS3A	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
RNPS1	C1orf226	psi-mi:“MI:0914”(association)	0.350
CDH5	NBAS	psi-mi:“MI:0914”(association)	0.350
MRFAP1L1	MYO9A	psi-mi:“MI:0914”(association)	0.350
CBX4	DPM1	psi-mi:“MI:0914”(association)	0.350
PCGF1	HSPD1	psi-mi:“MI:0914”(association)	0.350
PHC2	CBX4	psi-mi:“MI:0914”(association)	0.350
PHC3	CBX4	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), CDADC1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), SCML1 (Affinity Capture-MS)

ESM2 similar proteins: B0FZN7, B0FZN8, B0FZN9, B0FZP0, B0FZP1, B0FZP2, B0FZP3, O08750, O60381, P01105, P04150, P08235, P10157, P19102, P32314, P46200, Q08D88, Q0P4X6, Q16649, Q1LXZ9, Q29131, Q2KJ34, Q3UPW2, Q3YC04, Q4JM28, Q4V7E1, Q5DTV4, Q5FW38, Q5HYM0, Q5R7I3, Q5R9P5, Q5WM45, Q62661, Q66J36, Q66J77, Q68EL6, Q6NYU3, Q6XLJ0, Q8AYI2, Q8K402

Diamond homologs: B0FZN7, B0FZN8, B0FZN9, B0FZP0, B0FZP1, B0FZP2, B0FZP3, P78364, Q5DTW2, Q5VUG0, Q64028, Q80VG1, Q8CHP6, Q8K214, Q8N228, Q8NDX5, Q8QHL5, Q96GD3, Q9JMD1, Q9JMD2, Q9UHJ3, Q9UN30, Q9UQR0, Q9VHA0, Q9VK33, Q29L50, Q4V7W5, Q8IXK0, Q9QWH1, A2A5N8, B1B1A0, D3YUG0, D3YXK1, D3ZWK4, E1C2V1, I3L5V6, P39769, Q1RNF8, Q5VXD3, Q6SPE9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SUMOylation of DNA methylation proteins	6	122.1×	1e-09
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	7	63.8×	1e-09
SUMOylation of transcription cofactors	7	51.5×	3e-09
SUMOylation of RNA binding proteins	7	50.5×	3e-09
Regulation of PTEN gene transcription	7	37.9×	2e-08
SUMOylation of chromatin organization proteins	7	33.6×	4e-08
SUMOylation of DNA damage response and repair proteins	7	31.1×	6e-08
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	7	31.1×	6e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	6
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2424639	NC_000023.10:g.(?17393881)(18525300_?)del	Pathogenic

SpliceAI

1090 predictions. Top by Δscore:

Variant	Effect	Δscore
X:17737663:GC:G	donor_gain	1.0000
X:17737677:A:AG	donor_gain	1.0000
X:17745540:G:GG	donor_gain	1.0000
X:17749394:TAATA:T	acceptor_loss	1.0000
X:17749397:TAGGT:T	acceptor_loss	1.0000
X:17749398:A:AG	acceptor_gain	1.0000
X:17749398:A:C	acceptor_loss	1.0000
X:17749399:G:A	acceptor_loss	1.0000
X:17749399:G:GG	acceptor_gain	1.0000
X:17749502:CAT:C	donor_gain	1.0000
X:17749503:ATGTA:A	donor_loss	1.0000
X:17749504:TG:T	donor_loss	1.0000
X:17749505:G:GA	donor_loss	1.0000
X:17749506:TAAGT:T	donor_loss	1.0000
X:17749883:T:TA	acceptor_gain	1.0000
X:17749885:T:TA	acceptor_gain	1.0000
X:17749890:TCA:T	acceptor_loss	1.0000
X:17749891:CAG:C	acceptor_loss	1.0000
X:17749892:A:AG	acceptor_gain	1.0000
X:17749892:A:T	acceptor_loss	1.0000
X:17749893:G:A	acceptor_loss	1.0000
X:17749893:G:GA	acceptor_gain	1.0000
X:17749893:GA:G	acceptor_gain	1.0000
X:17749893:GAA:G	acceptor_gain	1.0000
X:17749893:GAAGC:G	acceptor_gain	1.0000
X:17750289:TTCAG:T	donor_loss	1.0000
X:17750290:TCAGG:T	donor_loss	1.0000
X:17750291:CAGG:C	donor_loss	1.0000
X:17750292:AGGTA:A	donor_loss	1.0000
X:17750293:GG:G	donor_loss	1.0000

AlphaMissense

2154 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:17751883:T:A	W258R	0.997
X:17751883:T:C	W258R	0.997
X:17753267:G:T	G289W	0.997
X:17753268:G:T	G289V	0.997
X:17753268:G:A	G289E	0.996
X:17751885:G:C	W258C	0.995
X:17751885:G:T	W258C	0.995
X:17751908:T:C	F266S	0.995
X:17753277:T:C	L292P	0.995
X:17751907:T:C	F266L	0.993
X:17751909:T:A	F266L	0.993
X:17751909:T:G	F266L	0.993
X:17753364:T:C	L321P	0.993
X:17751956:T:C	F282S	0.992
X:17753343:T:C	L314P	0.991
X:17753265:A:T	D288V	0.990
X:17753267:G:A	G289R	0.990
X:17753267:G:C	G289R	0.990
X:17753286:T:C	L295P	0.990
X:17753341:G:C	K313N	0.990
X:17753341:G:T	K313N	0.990
X:17751911:T:C	L267P	0.988
X:17753277:T:A	L292Q	0.988
X:17751884:G:C	W258S	0.987
X:17753339:A:G	K313E	0.987
X:17753266:C:A	D288E	0.985
X:17753266:C:G	D288E	0.985
X:17753277:T:G	L292R	0.985
X:17753283:T:C	L294P	0.985
X:17753286:T:A	L295H	0.985

dbSNP variants (sampled 300 via entrez): RS1000006818 (X:17740475 A>G), RS1000071516 (X:17738518 C>T), RS1000122345 (X:17751614 A>G), RS1000474142 (X:17748004 A>G,T), RS1000547783 (X:17740829 G>A,T), RS1000593221 (X:17736337 A>AC), RS1000608083 (X:17748486 A>G), RS1000705215 (X:17748919 A>G), RS1001144258 (X:17752889 A>G), RS1001279931 (X:17753604 A>G), RS1001380220 (X:17743165 C>T), RS1001817482 (X:17742963 G>A), RS1001895109 (X:17742762 G>A), RS1002081433 (X:17742565 T>G), RS1002224132 (X:17754960 T>G)

Disease associations

OMIM: gene MIM:300227 | disease phenotypes: MIM:300672

GenCC curated gene-disease

Mondo (1): developmental and epileptic encephalopathy, 2 (MONDO:0010396)

Orphanet (3): Early infantile developmental and epileptic encephalopathy (Orphanet:1934), West syndrome (Orphanet:3451), CDKL5-deficiency disorder (Orphanet:505652)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1520	Metabolite levels	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010418	triacylglycerol 52:6 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564064	CDKL5 deficiency disorder (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, affects expression, increases methylation, affects cotreatment	10
trichostatin A	increases expression, affects cotreatment	4
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cupric oxide	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression	1
MT19c compound	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Coal	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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