SMCP

Summary

SMCP (sperm mitochondria associated cysteine rich protein, HGNC:6962) is a protein-coding gene on chromosome 1q21.3, encoding Sperm mitochondrial-associated cysteine-rich protein (P49901). Involved in sperm motility.

Sperm mitochondria differ in morphology and subcellular localization from those of somatic cells. They are elongated, flattened, and arranged circumferentially to form a helical coiled sheath in the midpiece of the sperm flagellum. The protein encoded by this gene localizes to the capsule associated with the mitochondrial outer membranes and is thought to function in the organization and stabilization of the helical structure of the sperm’s mitochondrial sheath.

Source: NCBI Gene 4184 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_030663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6962
Approved symbol	SMCP
Name	sperm mitochondria associated cysteine rich protein
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163206
Ensembl biotype	protein_coding
OMIM	601148
Entrez	4184

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368765

RefSeq mRNA: 1 — MANE Select: NM_030663 NM_030663

CCDS: CCDS1029

Canonical transcript exons

ENST00000368765 — 2 exons

Exon	Start	End
ENSE00001447920	152884403	152885047
ENSE00001447921	152878322	152878446

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 99.83.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6520 / max 611.6712, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5325	0.6320	4
5324	0.0200	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.83	gold quality
male germ cell	CL:0000015	99.71	gold quality
right testis	UBERON:0004534	99.24	gold quality
left testis	UBERON:0004533	99.13	gold quality
adult organism	UBERON:0007023	96.84	gold quality
testis	UBERON:0000473	96.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.68	gold quality
diaphragm	UBERON:0001103	84.10	gold quality
type B pancreatic cell	CL:0000169	81.87	gold quality
olfactory bulb	UBERON:0002264	80.53	gold quality
hair follicle	UBERON:0002073	72.74	gold quality
buccal mucosa cell	CL:0002336	71.27	gold quality
tongue squamous epithelium	UBERON:0006919	69.61	gold quality
cauda epididymis	UBERON:0004360	69.00	gold quality
epithelial cell of pancreas	CL:0000083	68.91	gold quality
thymus	UBERON:0002370	66.46	gold quality
vastus lateralis	UBERON:0001379	66.05	gold quality
mucosa of urinary bladder	UBERON:0001259	65.76	gold quality
quadriceps femoris	UBERON:0001377	65.55	gold quality
CA1 field of hippocampus	UBERON:0003881	65.49	gold quality
upper arm skin	UBERON:0004263	65.40	gold quality
cervix squamous epithelium	UBERON:0006922	65.01	gold quality
lateral globus pallidus	UBERON:0002476	63.52	gold quality
cerebellar vermis	UBERON:0004720	63.50	gold quality
cardiac muscle of right atrium	UBERON:0003379	63.44	gold quality
myocardium	UBERON:0002349	63.42	gold quality
left ventricle myocardium	UBERON:0006566	62.92	gold quality
nasal cavity epithelium	UBERON:0005384	62.44	gold quality
kidney epithelium	UBERON:0004819	62.21	gold quality
frontal pole	UBERON:0002795	61.44	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	7419.45
E-HCAD-38	yes	4574.51
E-ANND-3	no	1.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting SMCP, 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-4778-3P	99.93	70.40	1818
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-626	98.89	66.21	762
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-1293	96.16	64.69	916
HSA-MIR-6726-5P	95.97	63.72	841
HSA-MIR-920	95.97	63.95	811
HSA-MIR-5591-5P	95.85	64.76	1002
HSA-MIR-4300	95.85	64.56	1003
HSA-MIR-6741-5P	93.86	63.06	437

Literature-anchored findings (GeneRIF, showing 2)

• The levels of SMCP mRNA in human are much lower than in other mammals. (PMID:16325371)
• the initiation results indicate that an ectopically expressed variant form of SMCP has a role in tumor initiation of CSCs/CICs and that the variant form of SMCP might be a novel CSC/CIC marker (PMID:24244262)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Sperm mitochondrial-associated cysteine-rich protein — P49901 (reviewed: P49901)

All UniProt accessions (2): P49901, Q5T7P5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in sperm motility. Its absence is associated with genetic background dependent male infertility. Infertility may be due to reduced sperm motility in the female reproductive tract and inability to penetrate the oocyte zona pellucida.

Subcellular location. Cytoplasm. Mitochondrion membrane.

Tissue specificity. Testis. Is selectively expressed in the spermatids of seminiferous tubules.

RefSeq proteins (1): NP_109588* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039347	SMCP	Family

UniProt features (13 total): repeat 7, compositionally biased region 2, region of interest 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49901-F1	45.16	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): GOBP_SINGLE_FERTILIZATION, CHANG_IMMORTALIZED_BY_HPV31_DN, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOCC_MITOCHONDRIAL_ENVELOPE, HOSHIDA_LIVER_CANCER_LATE_RECURRENCE_DN, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, MODULE_113, GOBP_FERTILIZATION, RIZKI_TUMOR_INVASIVENESS_3D_UP, chr1q21, MATZUK_SPERMATOZOA, MODULE_49, GOCC_ORGANELLE_ENVELOPE, GOBP_PENETRATION_OF_ZONA_PELLUCIDA

GO Biological Process (3): penetration of zona pellucida (GO:0007341), flagellated sperm motility (GO:0030317), single fertilization (GO:0007338)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial membrane (GO:0031966), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
single fertilization	1
multi-multicellular organism process	1
multicellular organismal reproductive process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
fertilization	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMCP	SELENOP	P49908	839
SMCP	AZU1	P20160	649
SMCP	TNP2	Q05952	571
SMCP	GPX2	P18283	565
SMCP	GPX3	P22352	548
SMCP	TXN	P10599	543
SMCP	ODF1	Q14990	541
SMCP	TNP1	P09430	506
SMCP	PRM2	P04554	506
SMCP	PRM1	P04553	447
SMCP	CPO	Q8IVL8	412
SMCP	AKAP4	Q5JQC9	393
SMCP	TEKT2	Q9UIF3	375
SMCP	S100A5	P33763	371
SMCP	YBX2	Q9Y2T7	369

IntAct

294 interactions, top by confidence:

A	B	Type	Score
KRTAP4-12	SMCP	psi-mi:“MI:0915”(physical association)	0.790
SMCP	KRTAP4-12	psi-mi:“MI:0915”(physical association)	0.790
SMCP	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.720
SMCP	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	SMCP	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	SMCP	psi-mi:“MI:0915”(physical association)	0.720
KRT31	SMCP	psi-mi:“MI:0915”(physical association)	0.720
SMCP	LCE4A	psi-mi:“MI:0915”(physical association)	0.720
SMCP	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.720
SMCP	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.720
SMCP	KRTAP4-11	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	SMCP	psi-mi:“MI:0915”(physical association)	0.720
SMCP	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
SMCP	KRT31	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (91): SMCP (Two-hybrid), SMCP (Two-hybrid), SMCP (Two-hybrid), TCF4 (Two-hybrid), CALCOCO2 (Two-hybrid), RGS17 (Two-hybrid), KRTAP4-12 (Two-hybrid), KRTAP9-2 (Two-hybrid), KRTAP9-4 (Two-hybrid), KRTAP4-7 (Two-hybrid), LCE4A (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTR4, A6QNZ4, O14633, O70554, O70555, O70556, O70557, O70558, O70559, O70560, O70562, P15265, P22528, P22531, P22532, P35321, P35322, P35323, P35324, P35325, P35326, P49901, Q28658, Q32L04, Q4KL71, Q4R956, Q5T5B0, Q5T750, Q5T752, Q5T754, Q5T870, Q5T871, Q5TA76, Q5TA77, Q5TA78, Q5TA79, Q5TA81, Q5TA82, Q5TCM9, Q62266

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 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
Keratinization	39	36.8×	4e-53
Formation of the cornified envelope	13	19.4×	2e-12

GO biological processes:

GO term	Partners	Fold	FDR
hair cycle	6	119.5×	6e-10
keratinization	12	59.8×	1e-16

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

89 predictions. Top by Δscore:

Variant	Effect	Δscore
1:152884401:A:AG	acceptor_gain	1.0000
1:152884402:G:GG	acceptor_gain	1.0000
1:152878442:ACCAG:A	donor_loss	0.9800
1:152878443:CCAG:C	donor_loss	0.9800
1:152878444:CAGG:C	donor_loss	0.9800
1:152878445:AGG:A	donor_loss	0.9800
1:152878446:GGTA:G	donor_loss	0.9800
1:152878447:G:A	donor_loss	0.9800
1:152878448:T:G	donor_loss	0.9800
1:152884398:TCTA:T	acceptor_loss	0.9700
1:152884399:CTAGT:C	acceptor_loss	0.9700
1:152884400:TA:T	acceptor_loss	0.9700
1:152884401:AGTA:A	acceptor_loss	0.9700
1:152884402:G:GT	acceptor_loss	0.9700
1:152884402:GT:G	acceptor_gain	0.9700
1:152884402:GTA:G	acceptor_gain	0.9700
1:152884402:GTAC:G	acceptor_gain	0.9700
1:152878402:G:GT	donor_gain	0.9400
1:152878406:TC:T	donor_gain	0.9200
1:152878368:G:GT	donor_gain	0.9100
1:152884402:GTACC:G	acceptor_gain	0.9000
1:152878622:G:GT	donor_gain	0.8800
1:152878415:G:GT	donor_gain	0.8300
1:152884389:T:G	acceptor_loss	0.8000
1:152878596:A:T	donor_gain	0.7900
1:152878416:A:T	donor_gain	0.7800
1:152884404:A:AG	acceptor_gain	0.7700
1:152878431:T:A	donor_gain	0.7100
1:152878595:G:GT	donor_gain	0.7100
1:152884400:TAGTA:T	acceptor_gain	0.7100

AlphaMissense

782 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:152884617:C:G	C65W	0.677
1:152884633:T:C	C71R	0.653
1:152884633:T:A	C71S	0.625
1:152884634:G:C	C71S	0.625
1:152884635:C:G	C71W	0.623
1:152884638:T:G	C72W	0.593
1:152884596:C:G	C58W	0.571

dbSNP variants (sampled 300 via entrez): RS1000198380 (1:152876704 C>CCT), RS1000494176 (1:152882578 A>G), RS1000793199 (1:152880950 G>A,T), RS1002654064 (1:152881176 A>G), RS1002869448 (1:152881454 C>A,T), RS1002915024 (1:152878318 G>A,T), RS1002964122 (1:152881253 G>C,T), RS1003093305 (1:152878578 T>C), RS1003209400 (1:152882420 G>T), RS1004101475 (1:152877075 G>T), RS1004153799 (1:152877334 G>A), RS1004335272 (1:152881612 C>T), RS1004339679 (1:152882937 C>T), RS1004429967 (1:152881484 C>G,T), RS1004547296 (1:152877330 A>T)

Disease associations

OMIM: gene MIM:601148 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007564_25	Asthma or allergic disease (pleiotropy)	5.000000e-09
GCST008916_87	Asthma	2.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Polychlorinated Biphenyls	affects expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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