SCAF8

Summary

SCAF8 (SR-related CTD associated factor 8, HGNC:20959) is a protein-coding gene on chromosome 6q25.2, encoding SR-related and CTD-associated factor 8 (Q9UPN6). Anti-terminator protein required to prevent early mRNA termination during transcription.

Enables RNA binding activity and RNA polymerase II C-terminal domain phosphoserine binding activity. Involved in negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled and positive regulation of DNA-templated transcription, elongation. Located in nucleoplasm.

Source: NCBI Gene 22828 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 176 total
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈9% of expected missense variation)
• GTEx eGene: eQTL in 19 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.28 (highly constrained)
• MANE Select transcript: NM_014892
• Interaction hub: 1,960 STRING partners (top 8% of genes corpus-wide)
• Notable: 176 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20959
Approved symbol	SCAF8
Name	SR-related CTD associated factor 8
Location	6q25.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1116
Ensembl gene	ENSG00000213079
Ensembl biotype	protein_coding
OMIM	616024
Entrez	22828

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000367178

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 2: 3, TSL 5: 3

ENST00000367178, ENST00000367186, ENST00000417268, ENST00000461219, ENST00000464628, ENST00000479234, ENST00000899496, ENST00000913266, ENST00000913267, ENST00000913268, ENST00000997053, ENST00001133587

RefSeq mRNA: 5 — MANE Select: NM_014892 NM_001286188, NM_001286189, NM_001286194, NM_001286199, NM_014892

CCDS: CCDS5247, CCDS69226, CCDS75541

Canonical transcript exons

ENST00000367178 — 20 exons

Exon	Start	End
ENSE00000813828	154795009	154795139
ENSE00000813830	154803544	154803623
ENSE00000813831	154805369	154805486
ENSE00000813833	154808686	154808798
ENSE00000813840	154824234	154824378
ENSE00000813842	154830922	154831140
ENSE00001190014	154818479	154818592
ENSE00001237676	154827172	154827240
ENSE00001237697	154822276	154822409
ENSE00001237706	154820177	154820333
ENSE00001237733	154810015	154810208
ENSE00001237750	154808070	154808201
ENSE00001237766	154801971	154802147
ENSE00001237781	154792823	154792976
ENSE00001375840	154815716	154815816
ENSE00001428900	154733416	154733930
ENSE00001812832	154831939	154834221
ENSE00003468077	154787861	154788022
ENSE00003563006	154773989	154774072
ENSE00003629300	154778001	154778045

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.9775 / max 416.4947, expressed in 1822 samples.

Highest expression (Bgee): secondary oocyte, oocyte, sperm, calcaneal tendon, caput epididymis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SCAF8 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 21 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	2.8e-07	+0.62	6:154634228:G:A
Nerve Tibial	eqtl	1.1e-06	+0.66	6:154634228:G:A
Adipose Subcutaneous	eqtl	3.6e-06	+0.63	6:154634228:G:A
Colon Transverse	eqtl	1.0e-04	+0.64	6:154613268:T:C
Adrenal Gland	eqtl	4.7e-04	+0.75	6:154653327:T:C
Esophagus Muscularis	eqtl	2.5e-03	+0.43	6:154613268:T:C
Muscle Skeletal	eqtl	4.9e-03	-0.23	6:154707928:AT:A
Cells EBV-transformed lymphocytes	eqtl	5.8e-03	+0.57	6:154486421:T:C
Spleen	eqtl	6.5e-03	+1.97	6:154971054:A:G
Testis	eqtl	6.6e-03	-0.13	6:154782116:A:G
Thyroid	eqtl	1.0e-02	+0.10	6:153912327:G:A
Brain Hippocampus	eqtl	1.2e-02	+0.97	6:155084792:T:C
Lung	eqtl	1.2e-02	+0.68	6:154457157:G:A
Whole Blood	eqtl	1.4e-02	-0.09	6:154780405:CAT:C
Esophagus Mucosa	eqtl	1.7e-02	+0.33	6:154988474:C:T
Cells Cultured fibroblasts	sqtl	2.5e-02	-1.02	6:153776434:A:G
Brain Amygdala	eqtl	2.7e-02	+0.92	6:155492742:C:A
Stomach	eqtl	2.8e-02	+0.17	6:153790566:T:C
Small Intestine Terminal Ileum	eqtl	2.9e-02	+0.76	6:154653327:T:C
Skin Sun Exposed Lower leg	sqtl	3.1e-02	+1.23	6:154478140:T:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
70675	37.1991	1819
70676	7.2302	1750
204264	2.0945	1099
70677	0.4537	208

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.59	gold quality
oocyte	CL:0000023	95.80	gold quality
sperm	CL:0000019	95.58	gold quality
calcaneal tendon	UBERON:0003701	94.91	gold quality
caput epididymis	UBERON:0004358	94.13	gold quality
cauda epididymis	UBERON:0004360	93.98	gold quality
male germ cell	CL:0000015	93.84	gold quality
upper leg skin	UBERON:0004262	93.80	gold quality
ventricular zone	UBERON:0003053	93.78	gold quality
corpus epididymis	UBERON:0004359	93.73	gold quality
colonic epithelium	UBERON:0000397	93.41	gold quality
synovial joint	UBERON:0002217	92.97	gold quality
pigmented layer of retina	UBERON:0001782	92.85	gold quality
choroid plexus epithelium	UBERON:0003911	92.74	gold quality
skin of hip	UBERON:0001554	92.42	gold quality
oral cavity	UBERON:0000167	92.36	gold quality
bronchial epithelial cell	CL:0002328	92.23	gold quality
seminal vesicle	UBERON:0000998	92.09	gold quality
mucosa of stomach	UBERON:0001199	92.05	gold quality
epithelium of mammary gland	UBERON:0003244	91.82	gold quality
corpus callosum	UBERON:0002336	91.59	gold quality
penis	UBERON:0000989	91.49	gold quality
mammary duct	UBERON:0001765	91.47	gold quality
ganglionic eminence	UBERON:0004023	91.37	gold quality
embryo	UBERON:0000922	91.26	gold quality
adrenal tissue	UBERON:0018303	91.16	gold quality
urethra	UBERON:0000057	91.09	gold quality
adult organism	UBERON:0007023	91.09	gold quality
sural nerve	UBERON:0015488	90.91	gold quality
parietal pleura	UBERON:0002400	90.88	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.88	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.83	gold quality
tibia	UBERON:0000979	90.60	gold quality
superficial temporal artery	UBERON:0001614	90.51	gold quality
cartilage tissue	UBERON:0002418	90.51	gold quality
biceps brachii	UBERON:0001507	90.46	gold quality
colonic mucosa	UBERON:0000317	90.13	gold quality
oviduct epithelium	UBERON:0004804	90.09	gold quality
bone marrow cell	CL:0002092	90.05	gold quality
jejunal mucosa	UBERON:0000399	89.95	gold quality
cortical plate	UBERON:0005343	89.93	gold quality
tibialis anterior	UBERON:0001385	89.44	gold quality
blood vessel layer	UBERON:0004797	89.43	gold quality
lower lobe of lung	UBERON:0008949	89.37	gold quality
esophagus squamous epithelium	UBERON:0006920	89.32	gold quality
endometrium	UBERON:0001295	89.16	gold quality
bone marrow	UBERON:0002371	89.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.12	gold quality
mammary gland	UBERON:0001911	89.09	gold quality
thoracic mammary gland	UBERON:0005200	89.09	gold quality
fallopian tube	UBERON:0003889	89.08	gold quality
epithelium of bronchus	UBERON:0002031	89.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.89	gold quality
bronchus	UBERON:0002185	88.85	gold quality
pleura	UBERON:0000977	88.83	gold quality
ovary	UBERON:0000992	88.81	gold quality
urinary bladder	UBERON:0001255	88.67	gold quality
trabecular bone tissue	UBERON:0002483	88.56	gold quality
jejunum	UBERON:0002115	88.33	gold quality
nasal cavity mucosa	UBERON:0001826	88.32	gold quality
layer of synovial tissue	UBERON:0007616	88.31	gold quality
islet of Langerhans	UBERON:0000006	88.30	gold quality
placenta	UBERON:0001987	88.24	gold quality
superior surface of tongue	UBERON:0007371	88.21	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.09	gold quality
female reproductive system	UBERON:0000474	87.76	gold quality
uterus	UBERON:0000995	87.74	gold quality
left ovary	UBERON:0002119	87.72	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.58	gold quality
epithelium of esophagus	UBERON:0001976	87.57	gold quality
connective tissue	UBERON:0002384	87.51	gold quality
adipose tissue	UBERON:0001013	87.50	gold quality
rectum	UBERON:0001052	87.48	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.41	gold quality
uterine cervix	UBERON:0000002	87.27	gold quality
zone of skin	UBERON:0000014	87.19	gold quality
lymph node	UBERON:0000029	87.15	gold quality
right ovary	UBERON:0002118	87.09	gold quality
tonsil	UBERON:0002372	87.07	gold quality
popliteal artery	UBERON:0002250	87.02	gold quality
tibial artery	UBERON:0007610	87.02	gold quality
left uterine tube	UBERON:0001303	86.96	gold quality
decidua	UBERON:0002450	86.94	gold quality
leukocyte	CL:0000738	86.90	gold quality
skeletal muscle tissue	UBERON:0001134	86.90	gold quality
muscle of leg	UBERON:0001383	86.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.84	gold quality
gastrocnemius	UBERON:0001388	86.81	gold quality
body of uterus	UBERON:0009853	86.80	gold quality
monocyte	CL:0000576	86.76	gold quality
mononuclear cell	CL:0000842	86.76	gold quality
tibial nerve	UBERON:0001323	86.68	gold quality
deltoid	UBERON:0001476	86.63	silver quality
endocervix	UBERON:0000458	86.58	gold quality
muscle tissue	UBERON:0002385	86.58	gold quality
hair follicle	UBERON:0002073	86.35	gold quality
skin of leg	UBERON:0001511	86.30	gold quality
skin of abdomen	UBERON:0001416	86.29	gold quality
muscle organ	UBERON:0001630	86.29	gold quality
myometrium	UBERON:0001296	86.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Nucleus accumbens	tissue	45.8
Cerebellum	tissue	43.9	high
Hippocampus	tissue	40.0	high
Postcentral gyrus	tissue	40.0
Locus coeruleus	tissue	36.1
Olfactory bulb	tissue	36.1
Bone marrow	tissue	35.1	high
Corpus callosum	tissue	34.7
Thalamus	tissue	32.7
Choroid plexus	tissue	32.3
Midbrain	tissue	32.3
Superior colliculi	tissue	31.9
Putamen	tissue	31.8
Cerebral cortex	tissue	31.7	high
Occipital cortex	tissue	31.7
Hypothalamus	tissue	31.1
Ventral forebrain	tissue	31.0
Somatosensory cortex	tissue	30.9
Spinal cord	tissue	30.6
Periaqueductal gray	tissue	30.6
Motor cortex	tissue	30.4
Substantia nigra	tissue	30.0
Septum	tissue	29.9
Prefrontal cortex	tissue	29.7
Hippocampal formation	tissue	29.7
Basal ganglia	tissue	29.6	high
Medulla oblongata	tissue	29.5
Retrosplenial cortex	tissue	29.2
Temporal cortex	tissue	29.2
Entorhinal cortex	tissue	29.0
Retrosplenial and cingulate cortex	tissue	28.9
Pons	tissue	28.8
Insular cortex	tissue	28.2
Amygdala	tissue	27.3
Caudate putamen	tissue	25.8
Thymus	tissue	25.0
Frontal cortex	tissue	23.3
Testis	tissue	22.0	high
Ovary	tissue	22.0	high
Retina	tissue	21.5
Lymph node	tissue	21.1	high
Endometrium 1	tissue	20.6	medium
Parathyroid gland	tissue	20.0	high
Thyroid gland	tissue	19.9	high
Tonsil	tissue	19.5	high
Smooth muscle	tissue	19.0	high
Spleen	tissue	18.0	high
Tongue	tissue	17.9
Breast	tissue	17.7	high
Placenta	tissue	17.7	high
Cervix	tissue	17.1	high
Rectum	tissue	16.5	high
Fallopian tube	tissue	16.4	high
Prostate	tissue	15.8	high
Skeletal muscle	tissue	15.6	high
Epididymis	tissue	15.5	high
Kidney	tissue	15.5	high
Lung	tissue	15.3	high
Seminal vesicle	tissue	14.7	high
Salivary gland	tissue	14.7	high

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Cerebellar cortex (63.3), Flocculonodular lobe (62.6), Vermis (60.1), Caudate nucleus (47.8), Area striata (white matter) (47.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting SCAF8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 84 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
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-4531	99.99	69.70	3181
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3658	99.96	73.87	4379
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-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.28, missense Z 1.19 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000367178 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈9% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
6:154,733,901–154,774,013	26 / 20.9	1.25	no
6:154,774,014–154,792,908	43 / 142.1	0.30	yes (p 9.5e-17)
6:154,792,909–154,815,730	339 / 407.5	0.83	no
6:154,815,731–154,820,253	59 / 110.7	0.53	no
6:154,820,254–154,833,392	930 / 874.6	1.06	no

Literature-anchored findings (GeneRIF, showing 2)

• SCAF8-CNKSR3 variant rs955333 was not associated with diabetic kidney disease but showed association with diabetic retinopathy in Chinese type 2 diabetes patients (PMID:28401168)
• Together, SCAF4 and SCAF8 coordinate the transition between elongation and termination, ensuring correct polyA site selection and RNAPII transcriptional termination in human cells. (PMID:31104839)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Scaf8	ENSMUSG00000046201
rattus_norvegicus	Scaf8	ENSRNOG00000016919
drosophila_melanogaster	Isha	FBGN0034598
caenorhabditis_elegans	nrd-1	WBGENE00017004

Paralogs (1): SCAF4 (ENSG00000156304)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1925212) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal embryo size	1
abnormal coat/hair pigmentation	1
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Arabidopsis thaliana	Q9SX80	94.0%	Diamond
Oryza sativa Japonica Group	Q5SNN4	90.9%	Diamond
Nicotiana plumbaginifolia	Q9LEB3	70.2%	Diamond
Candida albicans SC5314	Q59W50	60.1%	Diamond
Schizosaccharomyces pombe 972h-	O60176	48.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR1273C	ncRNA	100422821
TIAM2	protein-coding	26230
CLDN20	protein-coding	49861
NOX3	protein-coding	50508
TFB1M	protein-coding	51106

Protein

Protein identifiers

SR-related and CTD-associated factor 8 — Q9UPN6 (reviewed: Q9UPN6)

Alternative names: CDC5L complex-associated protein 7, RNA-binding motif protein 16

All UniProt accessions (2): A0A0A0MT33, Q9UPN6

UniProt curated annotations — full annotation on UniProt →

Function. Anti-terminator protein required to prevent early mRNA termination during transcription. Together with SCAF4, acts by suppressing the use of early, alternative poly(A) sites, thereby preventing the accumulation of non-functional truncated proteins. Mechanistically, associates with the phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit (POLR2A), and subsequently binds nascent RNA upstream of early polyadenylation sites to prevent premature mRNA transcript cleavage and polyadenylation. Independently of SCAF4, also acts as a positive regulator of transcript elongation.

Subunit / interactions. Interacts with POLR2A; via C-terminal heptapeptide repeat domain (CTD) phosphorylated at ‘Ser-2’ and ‘Ser-5’. Identified in a complex with CDC5L and other spliceosomal proteins.

Subcellular location. Nucleus. Nucleus matrix.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UPN6-1	1	yes
Q9UPN6-2	2

RefSeq proteins (5): NP_001273117, NP_001273118, NP_001273123, NP_001273128, NP_055707* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR006569	CID_dom	Domain
IPR008942	ENTH_VHS	Homologous_superfamily
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034370	SCAF8_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR051485	SR-CTD_assoc_factor	Family

Pfam: PF00076, PF04818

UniProt features (45 total): helix 11, compositionally biased region 10, modified residue 9, region of interest 6, domain 2, splice variant 2, chain 1, cross-link 1, sequence variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

10 structures by resolution:

PDB	Title	Method	Resolution (Å)
3D9J	Snapshots of the RNA processing factor SCAF8 bound to different phosphorylated forms of …	X-RAY DIFFRACTION	1.6
3D9N	Snapshots of the RNA processing factor SCAF8 bound to different phosphorylated forms of …	X-RAY DIFFRACTION	1.6
3D9M	Snapshots of the RNA processing factor SCAF8 bound to different phosphorylated forms of …	X-RAY DIFFRACTION	1.75
3D9I	Snapshots of the RNA processing factor SCAF8 bound to different phosphorylated forms of …	X-RAY DIFFRACTION	1.91
3D9O	Snapshots of the RNA processing factor SCAF8 bound to different phosphorylated forms of …	X-RAY DIFFRACTION	2
3D9P	Snapshots of the RNA processing factor SCAF8 bound to different phosphorylated forms of …	X-RAY DIFFRACTION	2.1
3D9K	Snapshots of the RNA processing factor SCAF8 bound to different phosphorylated forms of …	X-RAY DIFFRACTION	2.2
3D9L	Snapshots of the RNA processing factor SCAF8 bound to different phosphorylated forms of …	X-RAY DIFFRACTION	2.2
2DIW	Solution structure of the RPR domain of Putative RNA-binding protein 16	SOLUTION NMR
9U9X	1H, 13C, and 15N resonance assignments and solution structure of the CID domain of SCAF8 …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPN6-F1	52.01	0.17

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH enhanced · IF enhanced

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 (10)

Type	Positions
Phosphothreonine	6, 615
Phosphoserine	273, 617, 779
Asymmetric dimethylarginine	917, 927, 938, 1073
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	18

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 162 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, FREAC2_01, BROWNE_HCMV_INFECTION_6HR_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, chr6q25, KMCATNNWGGA_UNKNOWN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, ATTCTTT_MIR186, GOBP_TERMINATION_OF_RNA_POLYMERASE_II_TRANSCRIPTION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, AACTTT_UNKNOWN, GNF2_DDX5

GO Biological Process (3): termination of RNA polymerase II transcription (GO:0006369), positive regulation of DNA-templated transcription, elongation (GO:0032786), negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled (GO:2000805)

GO Molecular Function (7): RNA polymerase II complex binding (GO:0000993), RNA binding (GO:0003723), mRNA binding (GO:0003729), RNA polymerase core enzyme binding (GO:0043175), RNA polymerase II C-terminal domain phosphoserine binding (GO:1990269), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mRNA cleavage factor complex (GO:0005849), nuclear matrix (GO:0016363)

GO top-level categories

20 GO namespaces:

Category	Terms
cellular anatomical structure	3
binding	2
nuclear lumen	2
DNA-templated transcription termination	1
transcription by RNA polymerase II	1
DNA-templated transcription elongation	1
regulation of DNA-templated transcription elongation	1
positive regulation of DNA-templated transcription	1
termination of RNA polymerase II transcription, poly(A)-coupled	1
negative regulation of termination of RNA polymerase II transcription	1
regulation of termination of RNA polymerase II transcription, poly(A)-coupled	1
RNA polymerase core enzyme binding	1
nucleic acid binding	1
RNA binding	1
RNA polymerase binding	1
phosphoserine residue binding	1
RNA polymerase II C-terminal domain binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
nuclear protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of termination of RNA polymerase II transcription, poly(A)-coupled	BP	direct assay
positive regulation of DNA-templated transcription, elongation	BP	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	direct assay
RNA polymerase II C-terminal domain phosphoserine binding	MF	direct assay
RNA polymerase core enzyme binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,960 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCAF8	PCF11	O94913	720
SCAF8	RPRD1B	Q9NQG5	614
SCAF8	RPRD1A	Q96P16	572
SCAF8	RPRD2	Q5VT52	566
SCAF8	CNKSR3	Q6P9H4	532
SCAF8	SETX	Q7Z333	518
SCAF8	TFB1M	Q8WVM0	505
SCAF8	TIAM2	Q8IVF5	499
SCAF8	TULP4	Q9NRJ4	490
SCAF8	TMEM242	Q9NWH2	488
SCAF8	SERAC1	Q96JX3	488
SCAF8	GTF2H5	Q6ZYL4	476
SCAF8	NRDC	O43847	473
SCAF8	SCAF11	Q99590	472
SCAF8	SSU72	Q9NP77	451

IntAct

Human interaction partners of SCAF8 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
GOLGA2	physical association	0.670	4
DNPEP	physical association	0.590	2
GIGYF1	physical association	0.560	3
TEX11	physical association	0.560	3
HSPD1	physical association	0.400	1

BioGRID (96 interactions; top human partners by supporting records): CDC5L (Affinity Capture-MS; 3 records), FAM188A (Affinity Capture-MS; 3 records), DNPEP (Affinity Capture-MS; 2 records), JMJD6 (Affinity Capture-MS; 2 records), KLHL22 (Affinity Capture-MS; 2 records), MTUS2 (Affinity Capture-MS; 2 records), NAGK (Affinity Capture-MS; 2 records), TLE3 (Proximity Label-MS; 2 records), ACE2 (Proximity Label-MS), ALG13 (Proximity Label-MS), BMI1 (Affinity Capture-MS), CALML3 (Affinity Capture-MS), CELF1 (Proximity Label-MS), CHPF (Affinity Capture-MS), DDRGK1 (Affinity Capture-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ CDC5L complex	30	SRRM1, SF3B1, SRSF1, CDC5L, DYNC1H1, GCN1, HSPA8, PPP1CA, SF3B2, SCAF8, SNRPA, SRSF2, BZW1, RBMX, SFPQ, SNRPA1, SNRPD3, TCF4, PLRG1, SNRPD2, TOP2A, ILF2, SF3B4, SNRPD1, SFI1, BCAS2, CWC15, PPM1D, PRKDC, PRPF19

Disease & clinical

Genetic variants

Variant evidence for SCAF8: 176 ClinVar records (0 pathogenic / likely pathogenic); 9 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	145
Likely benign	6
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 43 predictions of 1,520):

Position(s)	Effect	Δscore	Sites
6:154733931–154733932	donor_loss	1.0000	5
6:154773987–154773988	acceptor_loss	1.0000	6
6:154774073–154774074	donor_loss	1.0000	2
6:154787842	acceptor_gain	1.0000
6:154788023–154788024	donor_loss	1.0000	4
6:154792821–154792822	acceptor_loss	1.0000	4
6:154795140–154795141	donor_loss	1.0000	5
6:154801969–154801970	acceptor_loss	1.0000	4
6:154803542–154803543	acceptor_loss	1.0000	6
6:154803624–154803625	donor_loss	1.0000	6

AlphaMissense

2,908 missense substitutions predicted likely pathogenic (of 8,286 scored), across 657 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M26	9	0.994	1.000
M519	9	0.975	1.000
M508	9	0.951	0.998
H42	8	1.000	1.000
D67	8	1.000	1.000
D82	8	1.000	1.000
H75	8	0.999	1.000
F7	8	0.998	1.000
F84	8	0.998	1.000
F88	8	0.998	1.000
F96	8	0.998	1.000
F123	8	0.998	1.000
N120	8	0.997	1.000
F77	8	0.996	1.000
D524	8	0.995	0.999
F50	8	0.994	1.000
N115	8	0.994	1.000
D591	8	0.992	0.998
D485	8	0.991	0.999
D226	8	0.987	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	9.69e-05
Breast Invasive Carcinoma (TCGA)	unfavorable	0.000234

Disease associations

OMIM: gene MIM:616024 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST008058_138	Estimated glomerular filtration rate	5e-15
GCST011494_60	Daytime nap	6e-12
GCST003127_9	Lipoprotein (a) levels	4e-10
GCST010043_101	Asthma	2e-9
GCST010042_77	Asthma	3e-9
GCST003098_3	Diabetic kidney disease	6e-9
GCST003209_5	Colorectal or endometrial cancer	2e-7
GCST008097_25	Bisphosphonate-associated atypical femoral fracture	2e-6
GCST001607_10	Renal function-related traits (eGRFcrea)	5e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0006925	lipoprotein A measurement
EFO:0004230	endometrial neoplasm
EFO:0009958	response to bisphosphonate
EFO:0009960	atypical femoral fracture
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	increases expression	2
Particulate Matter	decreases reaction, increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
sodium arsenite	affects expression	1
ochratoxin A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
jinfukang	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Caffeine	affects phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	increases methylation	1
Urethane	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00391261	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	Phase 3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	Phase 3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	Phase 3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	Phase 3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	Phase 3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	Phase 3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	Phase 3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	Phase 3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	Phase 3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder
NCT06333964	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of AST-001 in ASD Children
NCT07257939	Phase 3	NOT_YET_RECRUITING	NTI164 in Autism Spectrum Disorder
NCT07655115	Phase 3	RECRUITING	Single Dose Double-blind, Placebo-controlled Cross-over (SDDBPCCO) Shiftability Study, Will be Followed by a 10-week Open-label Study With Arbaclofen (4 Weeks of Titration and Then 6 Weeks of Active/Stable Treatment). The Effects of Arbaclofen on Target EEG and ERG Metrics Will be Associated With th
NCT00251303	Phase 2	COMPLETED	Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders
NCT00614198	Phase 2	COMPLETED	ScanBrit Dietary Intervention in Autism
NCT00619190	Phase 2	COMPLETED	Study of Aripiprazole to Treat Children and Adolescents With Autism
NCT00709202	Phase 2	COMPLETED	Efficacy and Tolerability Study of Betahistine to Ameliorate Antipsychotic Associated Weight Gain
NCT00846547	Phase 2	COMPLETED	Open-Label Study of the Safety and Tolerability of STX209 in Subjects With Autism Spectrum Disorders
NCT01064973	Phase 2	TERMINATED	An Open Label Extension Study of STX209 in Subjects With Autism Spectrum Disorders
NCT01170325	Phase 2	WITHDRAWN	A Study of Divalproex Sodium in Children With ASD and Epileptiform EEG
NCT01205282	Phase 2	COMPLETED	Dose Finding Study of Pioglitazone in Children With Autism Spectrum Disorders (ASD) (PIO)
NCT01248130	Phase 2	TERMINATED	Omega-3 Fatty Acids Monotherapy in Children and Adolescents With Autism Spectrum Disorders
NCT01248728	Phase 2	COMPLETED	Omega-3 Fatty Acids For Treatment Of Young Children With Autism (OMG)
NCT01256060	Phase 2	COMPLETED	Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY)
NCT01288716	Phase 2	COMPLETED	Study of Arbaclofen for the Treatment of Social Withdrawal in Subjects With Autism Spectrum Disorders
NCT01300923	Phase 2	COMPLETED	Acamprosate in Youth With Fragile X Syndrome
NCT01366859	Phase 2	COMPLETED	Nutritional Intervention in Children With Autism Using Whey Protein (Immunocal): Impact on Core Areas of Behavior
NCT01372449	Phase 2	COMPLETED	A Multi-site Double-blind Placebo-controlled Trial of Memantine Versus Placebo in Children With Autism (MEM)
NCT01395953	Phase 2	WITHDRAWN	Double-blind Trial of Buspirone for the Treatment of Anxiety in Youth With Autism Spectrum Disorders