SCAF1

Summary

SCAF1 (SR-related CTD associated factor 1, HGNC:30403) is a protein-coding gene on chromosome 19q13.3-q13.4, encoding Splicing factor, arginine/serine-rich 19 (Q9H7N4). May function in pre-mRNA splicing.

Enables RNA polymerase II C-terminal domain binding activity. Predicted to be involved in RNA splicing; mRNA processing; and transcription by RNA polymerase II. Predicted to be located in nucleus.

Source: NCBI Gene 58506 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 276 total
• MANE Select transcript: NM_021228

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30403
Approved symbol	SCAF1
Name	SR-related CTD associated factor 1
Location	19q13.3-q13.4
Locus type	gene with protein product
Status	Approved
Aliases	SR-A1, FLJ00034
Ensembl gene	ENSG00000126461
Ensembl biotype	protein_coding
OMIM	617264
Entrez	58506

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000360565, ENST00000595242, ENST00000598359, ENST00000601038, ENST00000892599, ENST00000892600, ENST00000892601

RefSeq mRNA: 1 — MANE Select: NM_021228 NM_021228

CCDS: CCDS33074

Canonical transcript exons

ENST00000360565 — 11 exons

Exon	Start	End
ENSE00000372244	49645354	49645411
ENSE00000720914	49646108	49646202
ENSE00000720919	49646526	49646626
ENSE00000720925	49646715	49646830
ENSE00000720934	49654349	49654431
ENSE00000720939	49654652	49654870
ENSE00001059235	49642209	49642242
ENSE00001375196	49645021	49645134
ENSE00001376701	49658208	49658642
ENSE00001387755	49650868	49653705
ENSE00001692656	49657761	49657889

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 94.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.6290 / max 113.7149, expressed in 1799 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177039	14.5262	1797
177041	0.3992	175
177038	0.3580	177
177040	0.3457	156

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	94.30	gold quality
right frontal lobe	UBERON:0002810	92.78	gold quality
anterior cingulate cortex	UBERON:0009835	92.28	gold quality
gastrocnemius	UBERON:0001388	91.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.47	gold quality
prefrontal cortex	UBERON:0000451	91.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.12	gold quality
stromal cell of endometrium	CL:0002255	90.97	gold quality
apex of heart	UBERON:0002098	90.92	gold quality
popliteal artery	UBERON:0002250	90.81	gold quality
tibial artery	UBERON:0007610	90.79	gold quality
muscle of leg	UBERON:0001383	90.74	gold quality
cortical plate	UBERON:0005343	90.62	gold quality
cerebellar hemisphere	UBERON:0002245	90.57	gold quality
cerebellar cortex	UBERON:0002129	90.49	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.37	gold quality
ganglionic eminence	UBERON:0004023	90.33	gold quality
left ventricle myocardium	UBERON:0006566	90.21	silver quality
amygdala	UBERON:0001876	90.10	gold quality
mucosa of stomach	UBERON:0001199	90.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.97	gold quality
ventricular zone	UBERON:0003053	89.96	gold quality
lower esophagus	UBERON:0013473	89.96	gold quality
aorta	UBERON:0000947	89.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.86	gold quality
body of uterus	UBERON:0009853	89.83	gold quality
adenohypophysis	UBERON:0002196	89.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.80	gold quality
monocyte	CL:0000576	89.44	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.22
E-GEOD-111727	no	505.03
E-MTAB-7606	no	217.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting SCAF1, 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-433-3P	99.98	69.37	1203
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-505-5P	97.01	65.54	778

Literature-anchored findings (GeneRIF, showing 7)

• This is the first study that examines the expression of the novel gene SR-A1 in colon cancer progression. (PMID:15493872)
• Our results suggest that SRA1 is associated with cancer progression and may possibly be characterized as a new marker of unfavorable prognosis for ovarian cancer. (PMID:16631123)
• This study unveils the presence of SR-A1, CD36, and LOX-1 in aortic valves and suggests potential mechanisms by which they may contribute to the pathological angiogenesis, inflammation, calcification, and lipid accumulation in AVS. (PMID:24929820)
• Study describes the discovery and cloning of fifteen novel splice variants of SCAF1 gene in cancer cells comprising a total of nine novel alternative splicing events between the annotated exons of the gene, producing seven novel SCAF1 transcripts with open-reading frames, and eight novel SCAF1 transcripts with premature termination codons that are likely long non-coding RNAs. Additionally, a novel 3’ UTR was discovered. (PMID:29787824)
• Analysis of the acrolein-modified sites of apolipoprotein B-100 in LDL. (PMID:32919080)
• SCAF1 drives the compositional diversity of mammalian respirasomes. (PMID:38575788)
• In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer. (PMID:38902237)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	scaf1	ENSDARG00000054010
mus_musculus	Scaf1	ENSMUSG00000038406
rattus_norvegicus	Scaf1	ENSRNOG00000056946
drosophila_melanogaster	CG2926	FBGN0037344

Paralogs (2): PHRF1 (ENSG00000070047), SCAF11 (ENSG00000139218)

Protein

Protein identifiers

Splicing factor, arginine/serine-rich 19 — Q9H7N4 (reviewed: Q9H7N4)

Alternative names: SR-related C-terminal domain-associated factor 1, SR-related-CTD-associated factor, Serine arginine-rich pre-mRNA splicing factor SR-A1

All UniProt accessions (4): Q9H7N4, M0R232, M0R2L3, M0R3G4

UniProt curated annotations — full annotation on UniProt →

Function. May function in pre-mRNA splicing.

Subunit / interactions. Interacts with POLR2A.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Highly expressed in fetal brain and liver, poorly expressed in salivary gland, heart, skin and ovary. Expressed in colorectal carcinomas and ovarian cancers. Overexpressed in colorectal carcinomas as compared to normal colonic mucosa.

Induction. Up-regulated by estrogens, androgens and glucocorticoids.

Similarity. Belongs to the splicing factor SR family.

RefSeq proteins (1): NP_067051* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR042841	SCAF1	Family
IPR057031	SFR19-like_C	Domain

Pfam: PF23030

UniProt features (66 total): compositionally biased region 29, modified residue 26, region of interest 6, sequence variant 2, chain 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7N4-F1	47.65	0.04

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 (27): 239, 335, 448, 453, 498, 500, 526, 548, 612, 614, 706, 719, 725, 732, 734, 738, 872, 874, 929, 936 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): TCCCCAC_MIR491, GOBP_RNA_SPLICING, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GOMF_RNA_POLYMERASE_BINDING, GOMF_RNA_POLYMERASE_CORE_ENZYME_BINDING, GOMF_BASAL_TRANSCRIPTION_MACHINERY_BINDING, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_WITH_H4K20ME1_MARK, DELACROIX_RARG_BOUND_MEF, GOBP_MRNA_PROCESSING, GOMF_RNA_POLYMERASE_II_C_TERMINAL_DOMAIN_BINDING, GSE14415_NATURAL_TREG_VS_TCONV_DN, ARID5B_TARGET_GENES, BARX1_TARGET_GENES, DLX6_TARGET_GENES

GO Biological Process (3): transcription by RNA polymerase II (GO:0006366), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (4): RNA binding (GO:0003723), protein domain specific binding (GO:0019904), RNA polymerase II C-terminal domain binding (GO:0099122), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
DNA-templated transcription	1
mRNA metabolic process	1
nucleic acid binding	1
protein binding	1
RNA polymerase II complex binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1290 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCAF1	POLG	P54098	580
SCAF1	SCAF8	Q9UPN6	553
SCAF1	COX6A1	P12074	539
SCAF1	COX7A2L	O14548	506
SCAF1	SCAF4	O95104	500
SCAF1	COX7A2	P14406	488
SCAF1	ACADS	P16219	447
SCAF1	PRR12	Q9ULL5	427
SCAF1	INSC	Q1MX18	382
SCAF1	SRSF7	Q16629	347
SCAF1	SEPTIN7	Q16181	319
SCAF1	CCNC	P24863	308
SCAF1	SCAI	Q8N9R8	299
SCAF1	LAMB4	A4D0S4	297
SCAF1	INTS15	Q96N11	290

IntAct

134 interactions, top by confidence:

A	B	Type	Score
POLR2J	POLR1C	psi-mi:“MI:0914”(association)	0.830
POLR2G	RECQL5	psi-mi:“MI:0914”(association)	0.730
POLR2D	MED19	psi-mi:“MI:0914”(association)	0.730
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
RPRD1B	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2J	POLR2D	psi-mi:“MI:0914”(association)	0.730
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
MEOX2	SCAF1	psi-mi:“MI:0915”(physical association)	0.560
CIB1	SCAF1	psi-mi:“MI:0915”(physical association)	0.560
GSC2	SCAF1	psi-mi:“MI:0915”(physical association)	0.560
MTSS2	SCAF1	psi-mi:“MI:0915”(physical association)	0.560
RTN4IP1	SCAF1	psi-mi:“MI:0915”(physical association)	0.560
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
ZBTB48	ZBTB24	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
SNRNP70	GTPBP1	psi-mi:“MI:0914”(association)	0.530
PAIP2B	CASC3	psi-mi:“MI:0914”(association)	0.530
RBM4	NVL	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530

BioGRID (165): SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Biochemical Activity), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS), SCAF1 (Affinity Capture-MS)

ESM2 similar proteins: A6H619, A6NFR6, A8MZF0, B1B0V2, H3BKT1, O08550, O08664, O15054, P08393, P0C674, P0DOD9, P0DPQ3, P14379, P18346, P28284, Q00587, Q0VBZ8, Q17QW1, Q32PF7, Q5NCY0, Q5U2Y8, Q5U4C3, Q5VV67, Q63003, Q63624, Q63625, Q66648, Q66HC8, Q6NZN1, Q6ZRT6, Q80U35, Q80WJ1, Q86UU5, Q86X51, Q8C1R3, Q8V7G4, Q8V7J2, Q8WUZ0, Q914N2, Q91W92

Diamond homologs: A1YVX4, A2A8L1, A2AUY4, A2BIL7, A6H619, A7E320, A8DZJ1, A9LMC0, B6CHA3, B7ZS37, B9RU15, C4QVX6, D3ZD32, E7EZF3, F4I240, F4JYC8, F4KE59, F6UA42, G5EBZ4, O43918, O88379, O94400, O97159, P29375, P41229, P41230, P46605, P47156, P48786, P56163, P58268, P58269, P58270, Q04996, Q09477, Q12830, Q12873, Q14839, Q23541, Q23590

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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
Transport of Mature Transcript to Cytoplasm	10	44.3×	3e-13
mRNA 3’-end processing	14	32.0×	4e-16
RNA Polymerase II Transcription Termination	10	25.5×	6e-11
Transport of Mature mRNA derived from an Intron-Containing Transcript	14	24.8×	1e-14
mRNA Splicing	19	24.3×	9e-20
Influenza Viral RNA Transcription and Replication	9	22.6×	2e-09
Pausing and recovery of Tat-mediated HIV elongation	5	21.4×	3e-05
Tat-mediated HIV elongation arrest and recovery	5	21.4×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	7	44.7×	2e-08
cytoplasmic translation	15	23.1×	6e-14
regulation of alternative mRNA splicing, via spliceosome	11	22.4×	5e-10
mRNA export from nucleus	8	19.7×	5e-07
ribosomal small subunit biogenesis	7	13.3×	6e-05
negative regulation of translation	7	11.4×	2e-04
translation	13	11.1×	2e-08
RNA splicing	15	11.0×	1e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	252
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

8316 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49651080:T:C	F231L	1.000
19:49651082:C:A	F231L	1.000
19:49651082:C:G	F231L	1.000
19:49651279:T:C	I297T	1.000
19:49651291:T:A	L301Q	1.000
19:49651291:T:C	L301P	1.000
19:49652467:T:C	L693P	1.000
19:49652491:T:A	I701N	1.000
19:49652491:T:C	I701T	1.000
19:49652503:T:A	I705N	1.000
19:49652503:T:C	I705T	1.000
19:49652503:T:G	I705S	1.000
19:49652893:C:T	S835F	1.000
19:49652897:G:C	K836N	1.000
19:49652897:G:T	K836N	1.000
19:49652908:T:C	L840P	1.000
19:49652985:T:C	F866L	1.000
19:49652986:T:C	F866S	1.000
19:49652987:C:A	F866L	1.000
19:49652987:C:G	F866L	1.000
19:49654358:T:A	L1109H	1.000
19:49654358:T:C	L1109P	1.000
19:49654361:T:A	L1110H	1.000
19:49654361:T:C	L1110P	1.000
19:49654363:T:C	F1111L	1.000
19:49654364:T:C	F1111S	1.000
19:49654365:C:A	F1111L	1.000
19:49654365:C:G	F1111L	1.000
19:49654370:T:G	M1113R	1.000
19:49654378:G:C	A1116P	1.000

dbSNP variants (sampled 300 via entrez): RS1000166903 (19:49649242 G>C), RS1000194092 (19:49648832 A>G,T), RS1000241123 (19:49642436 G>A), RS1000378568 (19:49655662 G>A,C), RS1000539579 (19:49658533 C>G,T), RS1000629462 (19:49649099 A>C), RS1000689819 (19:49642763 T>C,G), RS1000722274 (19:49643519 A>G), RS1000795650 (19:49653899 G>A), RS1001097370 (19:49657426 C>T), RS1001166964 (19:49648184 T>C), RS1001325441 (19:49652665 C>G,T), RS1001511612 (19:49655280 T>A,C), RS1001901816 (19:49656480 A>C), RS1001928509 (19:49651781 G>A)

Disease associations

OMIM: gene MIM:617264 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002539_91	Schizophrenia	5.000000e-08
GCST004785_16	Vitiligo	2.000000e-09
GCST006611_62	HDL cholesterol	2.000000e-09
GCST006803_99	Schizophrenia	4.000000e-11
GCST008871_6	Basal cell carcinoma	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Air Pollutants	increases abundance, increases expression, affects expression	2
aristolochic acid I	decreases expression, increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, increases methylation	1
lead acetate	increases expression	1
trichostatin A	affects expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Mustard Gas	increases phosphorylation	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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