SCOC

Summary

SCOC (short coiled-coil protein, HGNC:20335) is a protein-coding gene on chromosome 4q31.1, encoding Short coiled-coil protein (Q9UIL1). Positive regulator of amino acid starvation-induced autophagy.

This gene encodes a short coiled-coiled domain-containing protein that localizes to the Golgi apparatus. The encoded protein interacts with ADP-ribosylation factor-like proteins. Pseudogenes of this gene are found on chromosomes 1 and 14. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 60592 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_001153484

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20335
Approved symbol	SCOC
Name	short coiled-coil protein
Location	4q31.1
Locus type	gene with protein product
Status	Approved
Aliases	HRIHFB2072, SCOCO, UNC-69
Ensembl gene	ENSG00000153130
Ensembl biotype	protein_coding
Entrez	60592

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 34 protein_coding

ENST00000338517, ENST00000394203, ENST00000394205, ENST00000502535, ENST00000506322, ENST00000506597, ENST00000510586, ENST00000512749, ENST00000608372, ENST00000860187, ENST00000860188, ENST00000860189, ENST00000860190, ENST00000860191, ENST00000860192, ENST00000860193, ENST00000860194, ENST00000860195, ENST00000860196, ENST00000860197, ENST00000860198, ENST00000860199, ENST00000860200, ENST00000860201, ENST00000860202, ENST00000860203, ENST00000924238, ENST00000924239, ENST00000924240, ENST00000958255, ENST00000958256, ENST00000958257, ENST00000958258, ENST00000958259

RefSeq mRNA: 8 — MANE Select: NM_001153484 NM_001153446, NM_001153484, NM_001153552, NM_001153585, NM_001153635, NM_001153663, NM_001153690, NM_032547

CCDS: CCDS3750, CCDS54806, CCDS54807

Canonical transcript exons

ENST00000608372 — 4 exons

Exon	Start	End
ENSE00003707307	140379569	140379652
ENSE00003707441	140373646	140373717
ENSE00003708448	140380962	140385728
ENSE00003709164	140379121	140379192

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.0192 / max 1240.9486, expressed in 1791 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49793	36.2164	1777
49794	7.0237	1556
49792	0.4810	66
49791	0.1412	47
49786	0.1009	47
49785	0.0442	18
49784	0.0118	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.71	gold quality
substantia nigra pars compacta	UBERON:0001965	99.54	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.40	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.19	gold quality
superior vestibular nucleus	UBERON:0007227	99.16	gold quality
pons	UBERON:0000988	99.15	gold quality
lateral globus pallidus	UBERON:0002476	99.14	gold quality
subthalamic nucleus	UBERON:0001906	99.11	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.05	gold quality
medulla oblongata	UBERON:0001896	98.95	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.91	gold quality
left ventricle myocardium	UBERON:0006566	98.75	gold quality
hypothalamus	UBERON:0001898	98.67	gold quality
spinal cord	UBERON:0002240	98.65	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.60	gold quality
dorsal root ganglion	UBERON:0000044	98.59	gold quality
cerebellar vermis	UBERON:0004720	98.58	gold quality
midbrain	UBERON:0001891	98.53	gold quality
substantia nigra	UBERON:0002038	98.52	gold quality
myocardium	UBERON:0002349	98.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.33	gold quality
inferior vagus X ganglion	UBERON:0005363	98.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.27	gold quality
islet of Langerhans	UBERON:0000006	98.25	gold quality
prefrontal cortex	UBERON:0000451	98.22	gold quality
trigeminal ganglion	UBERON:0001675	98.21	gold quality
ventral tegmental area	UBERON:0002691	98.16	gold quality
kidney epithelium	UBERON:0004819	98.14	gold quality
pigmented layer of retina	UBERON:0001782	98.11	gold quality
nucleus accumbens	UBERON:0001882	97.94	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	23.74
E-MTAB-7316	yes	13.15
E-HCAD-5	no	8.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

113 targeting SCOC, 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-6876-5P	100.00	67.68	2126
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4753-3P	99.90	71.03	3786

Literature-anchored findings (GeneRIF, showing 5)

• The identification of SCOC and WAC as novel regulatory proteins with diverse functions in autophagy contributes towards a fuller understanding of autophagosome formation. (PMID:22354037)
• SCOC forms a stable homogeneous complex with the coiled coil domain of FEZ1. SCOC dimerization and the SCOC surface residue R117 are important for this interaction. (PMID:24098481)
• Studies indicate that FEZ1 (fasciculation and elongation protein zeta 1), SCOCO (short coiled-coil protein) and kinesins (kinesin heavy chain) are involved in biological transport process. (PMID:24116125)
• SCOC SNPs were associated with lifetime cannabis use, but the association did not reach genome-wide significance. [Meta-Analysis] (PMID:27023175)
• Phosphorylation of the LIR Domain of SCOC Modulates ATG8 Binding Affinity and Specificity. (PMID:33845085)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	scocb	ENSDARG00000002217
danio_rerio	scoca	ENSDARG00000087333
mus_musculus	Scoc	ENSMUSG00000063253
rattus_norvegicus	Scoc	ENSRNOG00000003853
drosophila_melanogaster	CG5934	FBGN0039505
caenorhabditis_elegans		WBGENE00006802

Protein

Protein identifiers

Short coiled-coil protein — Q9UIL1 (reviewed: Q9UIL1)

All UniProt accessions (3): Q9UIL1, A0A0C4DGB0, A0A804E055

UniProt curated annotations — full annotation on UniProt →

Function. Positive regulator of amino acid starvation-induced autophagy.

Subunit / interactions. Homodimer. Interacts with ARL1, ARL2 and ARL3. Directly interacts with FEZ1 and UVRAG. The interaction with UVRAG is reduced by amino acid starvation, but the complex is stabilized in the presence of FEZ1. Interacts with NRBF2.

Subcellular location. Golgi apparatus membrane. Golgi apparatus. trans-Golgi network. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed with highest levels in brain, heart and skeletal muscle.

Similarity. Belongs to the SCOC family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UIL1-1	1	yes
Q9UIL1-2	2
Q9UIL1-3	3
Q9UIL1-4	4

RefSeq proteins (8): NP_001146918, NP_001146956, NP_001147024, NP_001147057, NP_001147107, NP_001147135, NP_001147162, NP_115936 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019357	SCOC	Family

Pfam: PF10224

UniProt features (15 total): mutagenesis site 5, splice variant 4, sequence conflict 2, chain 1, coiled-coil region 1, turn 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7AA7	X-RAY DIFFRACTION	1.45
4BWD	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UIL1-F1	66.24	0.25

Functional residue map

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

Mutagenesis-validated functional residues (5):

Position	Phenotype
132	causes tetramerization and loss of interaction with fez1; when associated with l-125.
93	causes trimerization and impairs interaction with fez1 coiled coil but does not impair interaction with full-length fez1
97	causes trimerization and impairs interaction with fez1 coiled coil but does not impair interaction with full-length fez1
117	impairs interaction with fez1 coiled coil but does not impair interaction with full-length fez1.
125	causes tetramerization and loss of interaction with fez1; when associated with v-132.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic

MSigDB gene sets: 169 (showing top): RRAGTTGT_UNKNOWN, GOBP_REGULATION_OF_AUTOPHAGY, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, REACTOME_MEMBRANE_TRAFFICKING, AAAYRNCTG_UNKNOWN, GOBP_MACROAUTOPHAGY, SRF_Q5_01, SRF_01, MARTINEZ_RB1_TARGETS_UP, SRF_C, GOCC_TRANS_GOLGI_NETWORK, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, BACH2_01

GO Biological Process (2): positive regulation of macroautophagy (GO:0016239), regulation of protein complex stability (GO:0061635)

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

GO Cellular Component (8): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoplasm (GO:0005737), endosome (GO:0005768), trans-Golgi network (GO:0005802), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
endomembrane system	2
positive regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
regulation of biological quality	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
nuclear lumen	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasmic vesicle	1
Golgi apparatus subcompartment	1

Protein interactions and networks

STRING

826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCOC	FEZ1	Q99689	820
SCOC	KCNT2	Q6UVM3	680
SCOC	WAC	Q9BTA9	663
SCOC	ARL3	P36405	636
SCOC	ULK1	O75385	584
SCOC	FEZ2	Q9UHY8	566
SCOC	RAB3GAP1	Q15042	561
SCOC	UVRAG	Q9P2Y5	552
SCOC	C2orf80	Q0P641	527
SCOC	RAB3GAP2	Q9H2M9	527
SCOC	TTC12	Q9H892	525
SCOC	MGAT4D	A6NG13	506
SCOC	FAM89B	Q8N5H3	506
SCOC	ARFRP1	Q13795	505
SCOC	SLC66A2	Q8N2U9	497

IntAct

39 interactions, top by confidence:

A	B	Type	Score
FEZ1	SCOC	psi-mi:“MI:0915”(physical association)	0.700
SCOC	FEZ1	psi-mi:“MI:0403”(colocalization)	0.700
SCHIP1	SCOC	psi-mi:“MI:0915”(physical association)	0.690
SCOC	SCHIP1	psi-mi:“MI:0915”(physical association)	0.690
TCF4	SCOC	psi-mi:“MI:0915”(physical association)	0.560
KRT40	SCOC	psi-mi:“MI:0915”(physical association)	0.560
SCOC	TCF4	psi-mi:“MI:0915”(physical association)	0.560
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
Srgap2	SCOC	psi-mi:“MI:0915”(physical association)	0.400
SCOC	MAPK8	psi-mi:“MI:0915”(physical association)	0.370
ORF17	KPNA5	psi-mi:“MI:0914”(association)	0.350
ORF17.5	WWP2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HMGA1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
MAPRE1	SCAMP1	psi-mi:“MI:0914”(association)	0.350
NUMA1	SHANK3	psi-mi:“MI:0914”(association)	0.350
RPS6KA4	H1-0	psi-mi:“MI:0914”(association)	0.350
SCHIP1	VWA8	psi-mi:“MI:0914”(association)	0.350
FEZ1	POLRMT	psi-mi:“MI:0914”(association)	0.350
SCOC	SNAPIN	psi-mi:“MI:0914”(association)	0.350
BFSP2	NEK2	psi-mi:“MI:0914”(association)	0.350
FEZ1	KCNN4	psi-mi:“MI:0914”(association)	0.350

BioGRID (82): SCOC (Two-hybrid), KRT40 (Two-hybrid), SCOC (Affinity Capture-MS), SCOC (Co-fractionation), SCOC (Co-fractionation), SCOC (Two-hybrid), SCHIP1 (Affinity Capture-MS), C21orf91 (Affinity Capture-MS), FEZ2 (Affinity Capture-MS), SCOC (Affinity Capture-MS), TBC1D30 (Affinity Capture-MS), HEATR5A (Affinity Capture-MS), SASS6 (Affinity Capture-MS), GCC1 (Affinity Capture-MS), NRBF2 (Affinity Capture-MS)

ESM2 similar proteins: A4Q9F3, A8IHN8, D3YYI7, M0R7T9, O09112, O60347, O88751, P51509, Q09YL6, Q0IHH1, Q13202, Q13505, Q14190, Q147X3, Q17QD9, Q3TZ87, Q3UPL5, Q3V1H9, Q5TGI4, Q5VUJ9, Q5VV17, Q5XI57, Q61079, Q6A039, Q6PDS0, Q6ZVT0, Q7Z7K6, Q80UW0, Q86YJ5, Q8C4U2, Q8CES0, Q8N554, Q8N8J7, Q8TC41, Q8TDR2, Q8WWW0, Q96AQ8, Q96ET8, Q96KN8, Q96MM7

Diamond homologs: A8NJZ7, Q08BG7, Q5RJZ6, Q5XJK1, Q78YZ6, Q9UIL1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2020 predictions. Top by Δscore:

Variant	Effect	Δscore
4:140257406:GGAAG:G	donor_gain	1.0000
4:140257407:GAAG:G	donor_gain	1.0000
4:140257407:GAAGG:G	donor_gain	1.0000
4:140257411:G:GG	donor_gain	1.0000
4:140343705:ATAGG:A	donor_loss	1.0000
4:140343706:TAGG:T	donor_loss	1.0000
4:140343707:AGGTA:A	donor_loss	1.0000
4:140343708:GGTAA:G	donor_loss	1.0000
4:140343709:GTAAG:G	donor_loss	1.0000
4:140343710:T:A	donor_loss	1.0000
4:140379567:A:AG	acceptor_gain	1.0000
4:140379568:G:GG	acceptor_gain	1.0000
4:140379568:GC:G	acceptor_gain	1.0000
4:140379568:GCA:G	acceptor_gain	1.0000
4:140379648:TGAAG:T	donor_loss	1.0000
4:140379650:AAGG:A	donor_loss	1.0000
4:140379651:AGGT:A	donor_loss	1.0000
4:140379652:GGTT:G	donor_loss	1.0000
4:140379653:G:GA	donor_loss	1.0000
4:140379654:T:A	donor_loss	1.0000
4:140380957:T:G	acceptor_gain	1.0000
4:140380957:TATA:T	acceptor_loss	1.0000
4:140380958:ATAG:A	acceptor_loss	1.0000
4:140380959:T:G	acceptor_gain	1.0000
4:140380959:TAG:T	acceptor_loss	1.0000
4:140380960:A:AG	acceptor_gain	1.0000
4:140380960:A:C	acceptor_loss	1.0000
4:140380961:G:GA	acceptor_gain	1.0000
4:140380961:G:GT	acceptor_loss	1.0000
4:140380961:GAT:G	acceptor_gain	1.0000

AlphaMissense

1038 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:140381069:T:C	F149L	1.000
4:140381071:T:A	F149L	1.000
4:140381071:T:G	F149L	1.000
4:140379635:T:C	L107P	0.999
4:140380965:T:C	L114P	0.999
4:140381007:T:C	L128P	0.999
4:140381028:T:A	L135H	0.999
4:140381036:T:C	Y138H	0.999
4:140381037:A:G	Y138C	0.999
4:140381049:T:C	L142P	0.999
4:140381070:T:G	F149C	0.999
4:140379614:T:C	L100P	0.998
4:140379647:T:A	L111H	0.998
4:140380986:T:A	V121D	0.998
4:140381001:T:C	L126P	0.998
4:140381018:A:G	N132D	0.998
4:140381020:C:A	N132K	0.998
4:140381020:C:G	N132K	0.998
4:140381040:T:A	I139K	0.998
4:140381049:T:A	L142H	0.998
4:140380965:T:A	L114H	0.997
4:140380982:G:C	A120P	0.997
4:140380990:G:C	K122N	0.997
4:140380990:G:T	K122N	0.997
4:140381012:T:C	S130P	0.997
4:140381069:T:G	F149V	0.997
4:140381070:T:C	F149S	0.997
4:140379623:A:C	Q103P	0.996
4:140379647:T:C	L111P	0.996
4:140380999:T:A	N125K	0.996

dbSNP variants (sampled 300 via entrez): RS1000005162 (4:140294675 CTA>C), RS1000012045 (4:140340602 G>T), RS1000045911 (4:140296018 G>C,T), RS1000064272 (4:140287944 G>A), RS1000078209 (4:140341822 C>T), RS1000101398 (4:140289013 A>G), RS1000114731 (4:140313542 G>A), RS1000152837 (4:140381174 A>G), RS1000153980 (4:140313569 C>T), RS1000200570 (4:140270995 TTC>T), RS1000203510 (4:140264563 A>C), RS1000223101 (4:140361711 A>C), RS1000320584 (4:140374160 G>A), RS1000323095 (4:140359992 G>A), RS10003754 (4:140329988 G>A,T)

Disease associations

OMIM: gene `` | 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
GCST007327_112	Smoking status (ever vs never smokers)	2.000000e-09
GCST007327_138	Smoking status (ever vs never smokers)	4.000000e-09
GCST010725_4	Malaria	4.000000e-10
GCST010725_84	Malaria	7.000000e-11
GCST010725_89	Malaria	7.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance	2
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
bufotalin	increases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases methylation	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	increases methylation	1
jinfukang	decreases expression	1
picoxystrobin	decreases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Antimycin A	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	decreases expression	1

Clinical trials (associated diseases)

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