SSPN

Summary

SSPN (sarcospan, HGNC:11322) is a protein-coding gene on chromosome 12p12.1, encoding Sarcospan (Q14714). Component of the dystrophin-glycoprotein complex (DGC), a complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix.

This gene encodes a member of the dystrophin-glycoprotein complex (DGC). The DGC spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Two alternatively spliced transcript variants that encode different protein isoforms have been described.

Source: NCBI Gene 8082 — RefSeq curated summary.

At a glance

• GWAS associations: 124
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_005086

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11322
Approved symbol	SSPN
Name	sarcospan
Location	12p12.1
Locus type	gene with protein product
Status	Approved
Aliases	SPN1, SPN2
Ensembl gene	ENSG00000123096
Ensembl biotype	protein_coding
OMIM	601599
Entrez	8082

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000242729, ENST00000422622, ENST00000534829, ENST00000535504, ENST00000538142, ENST00000539019, ENST00000540266, ENST00000544231, ENST00000858023

RefSeq mRNA: 2 — MANE Select: NM_005086 NM_001135823, NM_005086

CCDS: CCDS44850, CCDS8707

Canonical transcript exons

ENST00000242729 — 3 exons

Exon	Start	End
ENSE00001704835	26230711	26234777
ENSE00001775981	26195573	26195951
ENSE00003664807	26224293	26224379

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0167 / max 90.2121, expressed in 1040 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124814	3.2207	752
124813	2.0961	774
124816	0.2922	163
124811	0.2032	46
124815	0.1860	93
124812	0.0185	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
synovial joint	UBERON:0002217	98.60	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.42	gold quality
body of tongue	UBERON:0011876	98.01	gold quality
urethra	UBERON:0000057	97.98	gold quality
saphenous vein	UBERON:0007318	97.70	gold quality
trigeminal ganglion	UBERON:0001675	97.66	gold quality
calcaneal tendon	UBERON:0003701	97.41	gold quality
vena cava	UBERON:0004087	96.99	gold quality
dorsal root ganglion	UBERON:0000044	96.98	gold quality
tibia	UBERON:0000979	96.88	gold quality
biceps brachii	UBERON:0001507	96.83	gold quality
lateral globus pallidus	UBERON:0002476	96.82	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.55	gold quality
mammary duct	UBERON:0001765	96.34	gold quality
nipple	UBERON:0002030	96.23	gold quality
vastus lateralis	UBERON:0001379	95.57	gold quality
epithelium of mammary gland	UBERON:0003244	95.37	gold quality
quadriceps femoris	UBERON:0001377	95.09	gold quality
pericardium	UBERON:0002407	95.08	gold quality
blood vessel layer	UBERON:0004797	95.07	gold quality
seminal vesicle	UBERON:0000998	94.84	gold quality
cartilage tissue	UBERON:0002418	94.84	gold quality
superior vestibular nucleus	UBERON:0007227	94.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.76	gold quality
tendon	UBERON:0000043	94.63	gold quality
germinal epithelium of ovary	UBERON:0001304	94.57	gold quality
superior surface of tongue	UBERON:0007371	94.41	gold quality
penis	UBERON:0000989	94.20	gold quality
skeletal muscle tissue	UBERON:0001134	94.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	52.54
E-GEOD-134144	yes	33.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BTF3

miRNA regulators (miRDB)

165 targeting SSPN, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-551B-5P	99.96	71.28	3493

Literature-anchored findings (GeneRIF, showing 9)

• Analysis of sarcospan as a candidate gene for congenital fibrosis of the extraocular muscles type 1. (PMID:11180757)
• Frequent polymorphism of peroxisome proliferator activated receptor gamma gene in colorectal cancer containing wild-type K-ras gene. (PMID:11956653)
• Sarcospan plays an important mechanical role in stabilizing the dystrophin-glycoprotein complex. (PMID:17311848)
• crystal structure of Imp beta (127-876) in complex SPN1 (1-65) at 2.8-A resolution reveals that Imp beta adopts an open conformation, which is unique for a functional Imp beta/cargo complex, and resembles the conformation of the Imp beta/RanGTP complex (PMID:18028944)
• decreased expression of sarcospan at the Fukuyama congenital muscular dystrophy myofiber surfaces. (PMID:18830929)
• Human SSPN in transgegnic mice directly interacts with utrophin-glycoprotein comlpex and functions to stabilize utrophin protein without increasing utrophin transcription. (PMID:18981229)
• Our data suggest TWIST1 and SSPN to be the functionally relevant androgenetic alopecia genes at the 7p21.1 and 12p12.1 risk loci, respectively. (PMID:27060448)
• When human SSPN is expressed at three-fold levels in mdx mice, this increase in adhesion complex abundance improves muscle membrane stability, preventing many of the histopathological changes associated with Duchenne muscular dystrophy (PMID:27798107)
• Data indicate that Sspn is an Nkx2-5 modifier gene. Complete loss of Sspn function does not cause heart defects but does increase the incidence of muscular ventricular septal defects (VSDs) in combination with an Nkx2-5 mutation. (PMID:28406175)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sspn	ENSDARG00000041747
mus_musculus	Sspn	ENSMUSG00000030255
rattus_norvegicus	Sspn	ENSRNOG00000001807
drosophila_melanogaster	CG1806	FBGN0030360

Protein

Protein identifiers

Sarcospan — Q14714 (reviewed: Q14714)

Alternative names: K-ras oncogene-associated protein, Kirsten-ras-associated protein

All UniProt accessions (3): Q14714, F5H0K2, F5H381

UniProt curated annotations — full annotation on UniProt →

Function. Component of the dystrophin-glycoprotein complex (DGC), a complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix. Preferentially associates with the sarcoglycan subcomplex of the DGC.

Subcellular location. Cell membrane. Sarcolemma. Postsynaptic cell membrane.

Tissue specificity. Isoform 1 is expressed exclusively in heart and skeletal muscle. Isoform 2 is expressed in heart, skeletal muscle, thymus, prostate, testis, ovary, small intestine, colon and spleen.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14714-1	1, SPN1	yes
Q14714-2	2, SPN2
Q14714-3	3

RefSeq proteins (2): NP_001129295, NP_005077* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain
IPR030429	Sarcospan	Family

Pfam: PF04103

UniProt features (17 total): topological domain 5, transmembrane region 4, splice variant 2, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14714-F1	74.41	0.46

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9913351	Formation of the dystrophin-glycoprotein complex (DGC)
R-HSA-1474244	Extracellular matrix organization
R-HSA-3000171	Non-integrin membrane-ECM interactions

MSigDB gene sets: 216 (showing top): YAATNRNNNYNATT_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_329, LHX3_01, CHANDRAN_METASTASIS_DN, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_MUSCLE_CONTRACTION, BLALOCK_ALZHEIMERS_DISEASE_UP, WTGAAAT_UNKNOWN, MODULE_99, BROWNE_HCMV_INFECTION_24HR_DN, GOBP_MUSCLE_SYSTEM_PROCESS, GOBP_SENSORY_ORGAN_DEVELOPMENT, MODULE_387

GO Biological Process (2): muscle contraction (GO:0006936), cell adhesion (GO:0007155)

GO Molecular Function (0):

GO Cellular Component (8): Golgi membrane (GO:0000139), plasma membrane (GO:0005886), dystrophin-associated glycoprotein complex (GO:0016010), transport vesicle (GO:0030133), sarcolemma (GO:0042383), postsynaptic membrane (GO:0045211), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Non-integrin membrane-ECM interactions	1
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
muscle system process	1
cellular process	1
Golgi apparatus	1
bounding membrane of organelle	1
membrane	1
cell periphery	1
glycoprotein complex	1
plasma membrane protein complex	1
endomembrane system	1
cytoplasmic vesicle	1
plasma membrane	1
synaptic membrane	1
postsynapse	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

833 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SSPN	DAG1	Q14118	997
SSPN	DMD	P11532	996
SSPN	SGCA	Q16586	991
SSPN	SGCD	Q92629	990
SSPN	DTNA	Q9Y4J8	990
SSPN	SGCG	Q13326	975
SSPN	UTRN	P46939	952
SSPN	SGCE	O43556	940
SSPN	SNTA1	Q13424	863
SSPN	SGCB	Q16585	787
SSPN	ITPR2	Q14571	781
SSPN	SNTB1	Q13884	745
SSPN	CAV3	P56539	741
SSPN	SGCZ	Q96LD1	720
SSPN	DRP2	Q13474	623

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SSPN	H1-2	psi-mi:“MI:0915”(physical association)	0.400
SSPN	SMO	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (4): SSPN (Proximity Label-MS), SSPN (Two-hybrid), SSPN (Reconstituted Complex), Supt6 (Reconstituted Complex)

ESM2 similar proteins: A0A1D5NY17, A4IF75, B2RVY9, B3SHH9, F6V1J6, O42281, O70578, P19518, P97707, Q06432, Q08CE6, Q08DE1, Q0D289, Q0V9E0, Q14714, Q2MJQ7, Q4R4Z3, Q4V922, Q5CZV0, Q5PRC1, Q5RDV7, Q5XGU1, Q62147, Q66IV3, Q68FV0, Q6AZD1, Q6P0C6, Q6R5J2, Q6ZP80, Q6ZUX7, Q7ZZL8, Q86WI0, Q8BGA2, Q8NBL3, Q8VHW3, Q8VHW4, Q8VHW7, Q8VHW8, Q91Y55, Q925N4

Diamond homologs: P82352, Q14714, Q62147

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BTF3	“down-regulates quantity by repression”	SSPN	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1210 predictions. Top by Δscore:

Variant	Effect	Δscore
12:26123629:CCATT:C	donor_gain	1.0000
12:26123737:AGAGT:A	acceptor_gain	1.0000
12:26123738:GAGT:G	acceptor_gain	1.0000
12:26123740:GT:G	acceptor_gain	1.0000
12:26123741:TCTGC:T	acceptor_loss	1.0000
12:26123742:C:CC	acceptor_gain	1.0000
12:26123745:C:CT	acceptor_gain	1.0000
12:26123746:A:T	acceptor_gain	1.0000
12:26123747:G:C	acceptor_gain	1.0000
12:26123747:G:GC	acceptor_gain	1.0000
12:26123750:G:C	acceptor_gain	1.0000
12:26123750:G:GC	acceptor_gain	1.0000
12:26123753:C:CT	acceptor_gain	1.0000
12:26123754:A:T	acceptor_gain	1.0000
12:26124070:A:AC	donor_gain	1.0000
12:26124071:C:CC	donor_gain	1.0000
12:26124196:CA:C	acceptor_gain	1.0000
12:26124197:A:AC	acceptor_gain	1.0000
12:26124197:A:C	acceptor_gain	1.0000
12:26124512:CA:C	donor_gain	1.0000
12:26124517:A:AC	donor_gain	1.0000
12:26124517:AC:A	donor_gain	1.0000
12:26124518:C:CC	donor_gain	1.0000
12:26124518:CC:C	donor_gain	1.0000
12:26199895:G:GG	donor_gain	1.0000
12:26224376:GAAA:G	donor_gain	1.0000
12:26224380:G:GG	donor_gain	1.0000
12:26224989:G:T	donor_gain	1.0000
12:26225163:A:G	acceptor_gain	1.0000
12:26230710:GCT:G	acceptor_gain	1.0000

AlphaMissense

1570 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:26230729:A:C	S129R	0.990
12:26230731:T:A	S129R	0.990
12:26230731:T:G	S129R	0.990
12:26195937:T:A	W89R	0.989
12:26195937:T:C	W89R	0.989
12:26195883:G:C	G71R	0.987
12:26230993:T:A	W217R	0.987
12:26230993:T:C	W217R	0.987
12:26195862:G:C	G64R	0.984
12:26195943:G:T	G91W	0.984
12:26195904:A:C	S78R	0.981
12:26195906:C:A	S78R	0.981
12:26195906:C:G	S78R	0.981
12:26224296:T:C	C95R	0.981
12:26224368:T:C	F119L	0.981
12:26224370:T:A	F119L	0.981
12:26224370:T:G	F119L	0.981
12:26195943:G:A	G91R	0.980
12:26195943:G:C	G91R	0.980
12:26224314:G:C	G101R	0.978
12:26230768:T:C	F142L	0.977
12:26230770:T:A	F142L	0.977
12:26230770:T:G	F142L	0.977
12:26230950:T:A	N202K	0.976
12:26230950:T:G	N202K	0.976
12:26230995:G:C	W217C	0.976
12:26230995:G:T	W217C	0.976
12:26195944:G:A	G91E	0.975
12:26195884:G:A	G71D	0.974
12:26231014:T:C	F224L	0.974

dbSNP variants (sampled 300 via entrez): RS1000004037 (12:26205166 C>A,T), RS1000006207 (12:26174140 A>C), RS1000010744 (12:26159946 T>C), RS1000064647 (12:26127799 A>G), RS1000087411 (12:26178962 C>T), RS1000136740 (12:26134924 C>G), RS1000152105 (12:26123890 A>G), RS1000166549 (12:26180348 AT>A,ATT), RS1000184821 (12:26231890 G>A,T), RS1000197845 (12:26226334 G>C), RS1000204354 (12:26136510 G>A,C,T), RS1000229361 (12:26231886 C>A,T), RS1000264657 (12:26121140 G>C), RS1000363199 (12:26191634 G>C), RS1000364532 (12:26160291 T>A,G)

Disease associations

OMIM: gene MIM:601599 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

124 associations (top):

Study	Trait	p-value
GCST000829_5	Waist-hip ratio	1.000000e-17
GCST002782_53	Waist-to-hip ratio adjusted for body mass index	6.000000e-15
GCST002782_54	Waist-to-hip ratio adjusted for body mass index	4.000000e-16
GCST002782_55	Waist-to-hip ratio adjusted for body mass index	5.000000e-15
GCST002782_56	Waist-to-hip ratio adjusted for body mass index	2.000000e-15
GCST003983_22	Male-pattern baldness	4.000000e-12
GCST004064_4	Waist-hip ratio	2.000000e-11
GCST004064_40	Waist-hip ratio	6.000000e-12
GCST004505_62	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-13
GCST004505_63	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	9.000000e-16
GCST004507_15	Waist-to-hip ratio adjusted for BMI (joint analysis main effects and smoking interaction)	5.000000e-06
GCST004508_10	Waist-to-hip ratio adjusted for BMI in non-smokers	2.000000e-06
GCST004562_144	Waist circumference adjusted for body mass index	4.000000e-09
GCST004562_243	Waist circumference adjusted for body mass index	1.000000e-09
GCST004563_126	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	8.000000e-09
GCST004563_205	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	7.000000e-09
GCST004563_21	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-08
GCST004564_217	Waist circumference adjusted for BMI in active individuals	3.000000e-06
GCST004564_218	Waist circumference adjusted for BMI in active individuals	1.000000e-07
GCST004564_219	Waist circumference adjusted for BMI in active individuals	2.000000e-06
GCST004567_10	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	4.000000e-16
GCST004567_102	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	2.000000e-16
GCST004567_29	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	6.000000e-17
GCST004567_91	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	4.000000e-18
GCST004576_101	Waist-to-hip ratio adjusted for body mass index	6.000000e-18
GCST004576_138	Waist-to-hip ratio adjusted for body mass index	4.000000e-19
GCST004576_14	Waist-to-hip ratio adjusted for body mass index	3.000000e-18
GCST004576_53	Waist-to-hip ratio adjusted for body mass index	3.000000e-17
GCST004578_138	Waist-to-hip ratio adjusted for BMI in active individuals	1.000000e-14
GCST004578_42	Waist-to-hip ratio adjusted for BMI in active individuals	3.000000e-15

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004318	smoking behavior
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009270	heel bone mineral density
EFO:0006939	cup-to-disc ratio measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004462	PR interval
EFO:0008039	BMI-adjusted hip circumference
EFO:0004587	lymphocyte count
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression, affects expression	5
sodium arsenite	decreases expression, affects cotreatment	3
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression, affects cotreatment	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
lead acetate	affects cotreatment, decreases expression	1
terbufos	increases methylation	1
trichostatin A	decreases expression	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	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
belinostat	decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MRK 003	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Calcitriol	decreases expression	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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