SCFD2

Summary

SCFD2 (sec1 family domain containing 2, HGNC:30676) is a protein-coding gene on chromosome 4q12, encoding Sec1 family domain-containing protein 2 (Q8WU76). May be involved in protein transport.

Predicted to be involved in intracellular protein transport and vesicle-mediated transport.

Source: NCBI Gene 152579 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 102 total — 1 likely-pathogenic
• MANE Select transcript: NM_152540

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30676
Approved symbol	SCFD2
Name	sec1 family domain containing 2
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	STXBP1L1, FLJ39514
Ensembl gene	ENSG00000184178
Ensembl biotype	protein_coding
Entrez	152579

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000388940, ENST00000401642, ENST00000503450, ENST00000910196

RefSeq mRNA: 1 — MANE Select: NM_152540 NM_152540

CCDS: CCDS33984

Canonical transcript exons

ENST00000401642 — 9 exons

Exon	Start	End
ENSE00001303059	53313636	53313763
ENSE00001313844	52885747	52885866
ENSE00001322067	53145333	53145582
ENSE00001327240	53273826	53274001
ENSE00001504444	52907457	52907591
ENSE00001504446	52920725	52920870
ENSE00002052037	53365104	53366061
ENSE00002078201	52872982	52874061
ENSE00003623206	53352598	53352766

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 91.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.3773 / max 117.4627, expressed in 1777 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52122	10.7396	1771
52121	0.5085	262
52120	0.1292	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	91.38	silver quality
ileal mucosa	UBERON:0000331	90.92	gold quality
tibialis anterior	UBERON:0001385	90.20	silver quality
kidney epithelium	UBERON:0004819	90.13	silver quality
endothelial cell	CL:0000115	88.55	gold quality
deltoid	UBERON:0001476	88.28	silver quality
epithelial cell of pancreas	CL:0000083	88.23	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.93	gold quality
pericardium	UBERON:0002407	85.91	gold quality
stromal cell of endometrium	CL:0002255	85.65	gold quality
bone marrow cell	CL:0002092	85.32	gold quality
myocardium	UBERON:0002349	85.01	silver quality
nipple	UBERON:0002030	84.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.76	gold quality
pons	UBERON:0000988	84.69	gold quality
biceps brachii	UBERON:0001507	84.14	gold quality
superior vestibular nucleus	UBERON:0007227	84.10	gold quality
monocyte	CL:0000576	83.96	gold quality
nasal cavity epithelium	UBERON:0005384	83.95	silver quality
middle temporal gyrus	UBERON:0002771	83.86	gold quality
inferior vagus X ganglion	UBERON:0005363	83.85	gold quality
lower lobe of lung	UBERON:0008949	83.72	gold quality
left ventricle myocardium	UBERON:0006566	83.67	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.56	gold quality
leukocyte	CL:0000738	83.55	gold quality
islet of Langerhans	UBERON:0000006	83.54	gold quality
cardiac muscle of right atrium	UBERON:0003379	83.45	gold quality
skin of hip	UBERON:0001554	83.34	gold quality
ventral tegmental area	UBERON:0002691	83.24	gold quality
dorsal root ganglion	UBERON:0000044	83.17	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-7	no	29.11
E-ENAD-21	no	29.11
E-ANND-3	no	3.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

36 targeting SCFD2, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-4640-5P	97.42	66.33	1543

Literature-anchored findings (GeneRIF, showing 2)

• PSF Promotes ER-Positive Breast Cancer Progression via Posttranscriptional Regulation of ESR1 and SCFD2. (PMID:32213542)
• PSPC1 is a potential prognostic marker for hormone-dependent breast cancer patients and modulates RNA processing of ESR1 and SCFD2. (PMID:35681031)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	scfd2	ENSDARG00000040005
danio_rerio	si:ch73-249k16.4	ENSDARG00000093336
danio_rerio		ENSDARG00000115492
mus_musculus	Scfd2	ENSMUSG00000062110
rattus_norvegicus	Scfd2	ENSRNOG00000026828
caenorhabditis_elegans		WBGENE00020298

Paralogs (7): STXBP2 (ENSG00000076944), SCFD1 (ENSG00000092108), STXBP3 (ENSG00000116266), VPS45 (ENSG00000136631), STXBP1 (ENSG00000136854), VPS33A (ENSG00000139719), VPS33B (ENSG00000184056)

Protein

Protein identifiers

Sec1 family domain-containing protein 2 — Q8WU76 (reviewed: Q8WU76)

Alternative names: Syntaxin-binding protein 1-like 1

All UniProt accessions (2): D6RCK6, Q8WU76

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in protein transport.

Similarity. Belongs to the STXBP/unc-18/SEC1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WU76-1	1	yes
Q8WU76-2	2

RefSeq proteins (1): NP_689753* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001619	Sec1-like	Family
IPR027482	Sec1-like_dom2	Homologous_superfamily
IPR036045	Sec1-like_sf	Homologous_superfamily

Pfam: PF00995

UniProt features (3 total): chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WU76-F1	92.33	0.83

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, USF_C, COUP_01, WEI_MYCN_TARGETS_WITH_E_BOX, CREB_Q3, MORI_PLASMA_CELL_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, OSMAN_BLADDER_CANCER_DN, GRYDER_PAX3FOXO1_TOP_ENHANCERS, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_E2F4_UNSTIMULATED, SCGGAAGY_ELK1_02, KIM_MYCN_AMPLIFICATION_TARGETS_UP

GO Biological Process (3): intracellular protein transport (GO:0006886), vesicle-mediated transport (GO:0016192), protein transport (GO:0015031)

GO Molecular Function (0):

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	2
transport	2
protein transport	1
intracellular transport	1
cellular process	1
establishment of protein localization	1

Protein interactions and networks

STRING

612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCFD2	COG4	Q9H9E3	631
SCFD2	SCFD1	Q8WVM8	616
SCFD2	LNX1	Q8TBB1	566
SCFD2	FIP1L1	Q6UN15	529
SCFD2	RINT1	Q6NUQ1	503
SCFD2	STX18	Q9P2W9	458
SCFD2	ZW10	O43264	416
SCFD2	PLEKHA6	Q9Y2H5	372
SCFD2	CHIC2	Q9UKJ5	367
SCFD2	TRIML1	Q8N9V2	358
SCFD2	NBAS	A2RRP1	352
SCFD2	GSX2	Q9BZM3	333
SCFD2	DENND10	Q8TCE6	331
SCFD2	TMEM47	Q9BQJ4	329
SCFD2	LANCL2	Q9NS86	328

IntAct

55 interactions, top by confidence:

A	B	Type	Score
RINT1	NBAS	psi-mi:“MI:0914”(association)	0.830
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
BNIP1	NBAS	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
Zw10	NBAS	psi-mi:“MI:0914”(association)	0.560
Zw10	NBAS	psi-mi:“MI:0915”(physical association)	0.560
NAPA	NBAS	psi-mi:“MI:0914”(association)	0.530
VAMP5	NBAS	psi-mi:“MI:0914”(association)	0.530
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
VAMP4	NBAS	psi-mi:“MI:0914”(association)	0.350
SEC22B	NBAS	psi-mi:“MI:0914”(association)	0.350
RINT1	NBAS	psi-mi:“MI:0914”(association)	0.350
STX12	NBAS	psi-mi:“MI:0914”(association)	0.350
SCFD2	NBAS	psi-mi:“MI:0914”(association)	0.350
NAPG	NBAS	psi-mi:“MI:0914”(association)	0.350
USE1	NBAS	psi-mi:“MI:0914”(association)	0.350
SIRT2	DEGS1	psi-mi:“MI:0914”(association)	0.350
	NBAS	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350

BioGRID (77): SCFD2 (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), NBAS (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), BNIP1 (Affinity Capture-MS), ZW10 (Affinity Capture-MS), C19orf25 (Affinity Capture-MS), SCFD2 (Affinity Capture-MS), SCFD2 (Affinity Capture-MS)

ESM2 similar proteins: A0JM23, A2CEI4, A2RRP1, A4IHY1, A7RV13, B0DOB4, B1WC10, B5DF07, F6U5F9, O75153, O75800, O76024, P0CI65, P0DKR2, P42695, P56695, P57075, P97587, Q05AX3, Q08CY4, Q08D69, Q2I0E5, Q3U821, Q3URV1, Q566H4, Q5FWU8, Q5SW19, Q5TYW4, Q5U1Z0, Q5U249, Q6AXZ5, Q6AZT7, Q6DFC6, Q6DG91, Q6GPP1, Q6PGF3, Q6ZS30, Q7TNH6, Q7Z494, Q8BMG7

Diamond homologs: Q8BTY8, Q8WU76

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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
COPI-dependent Golgi-to-ER retrograde traffic	8	35.5×	3e-09
COPII-mediated vesicle transport	5	32.6×	5e-06
Golgi-to-ER retrograde transport	6	31.9×	1e-06
ER to Golgi Anterograde Transport	5	26.6×	1e-05
Intra-Golgi and retrograde Golgi-to-ER traffic	6	25.1×	3e-06
Transport to the Golgi and subsequent modification	5	20.6×	4e-05
Asparagine N-linked glycosylation	5	12.0×	5e-04
Membrane Trafficking	8	11.9×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	7	81.3×	4e-10
intracellular protein transport	5	11.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	88
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2571617	NM_152540.4(SCFD2):c.1148C>T (p.Pro383Leu)	Likely pathogenic

SpliceAI

5263 predictions. Top by Δscore:

Variant	Effect	Δscore
4:53145578:ATGCT:A	acceptor_gain	1.0000
4:53145579:TGCT:T	acceptor_gain	1.0000
4:53145581:CT:C	acceptor_gain	1.0000
4:53145583:C:CC	acceptor_gain	1.0000
4:53145588:A:AC	acceptor_gain	1.0000
4:53147268:T:TA	donor_gain	1.0000
4:53189130:T:A	donor_gain	1.0000
4:53212453:CAAAT:C	acceptor_gain	1.0000
4:53212457:T:TC	acceptor_gain	1.0000
4:53273821:CATA:C	donor_loss	1.0000
4:53273822:ATAC:A	donor_loss	1.0000
4:53273823:TA:T	donor_loss	1.0000
4:53273825:C:CT	donor_loss	1.0000
4:53273998:CTCC:C	acceptor_gain	1.0000
4:53274000:CC:C	acceptor_gain	1.0000
4:53274001:CC:C	acceptor_gain	1.0000
4:53274001:CCT:C	acceptor_loss	1.0000
4:53274002:C:CC	acceptor_gain	1.0000
4:53274002:CTGG:C	acceptor_loss	1.0000
4:53274003:T:A	acceptor_loss	1.0000
4:53313644:AT:A	donor_gain	1.0000
4:53313645:T:C	donor_gain	1.0000
4:53313759:TGTCA:T	acceptor_gain	1.0000
4:53313760:GTCA:G	acceptor_gain	1.0000
4:53313761:TCA:T	acceptor_gain	1.0000
4:53313762:CA:C	acceptor_gain	1.0000
4:53313762:CAC:C	acceptor_gain	1.0000
4:53313763:AC:A	acceptor_loss	1.0000
4:53313764:C:CC	acceptor_gain	1.0000
4:53313764:C:CG	acceptor_loss	1.0000

AlphaMissense

4438 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:53313683:A:G	L363P	0.999
4:52907464:A:G	F612S	0.998
4:52907473:A:G	F609S	0.996
4:52907482:T:A	K606I	0.996
4:53313692:C:G	R360P	0.996
4:53365133:A:T	V270D	0.996
4:52907481:T:A	K606N	0.995
4:52907481:T:G	K606N	0.995
4:53273980:A:G	L386P	0.995
4:53313671:G:T	A367E	0.995
4:53313708:C:G	A355P	0.995
4:53313712:T:A	K353N	0.995
4:53313712:T:G	K353N	0.995
4:53313713:T:A	K353I	0.995
4:52907464:A:C	F612C	0.994
4:52907476:C:T	G608E	0.994
4:52907485:A:T	L605H	0.994
4:53273902:G:T	A412D	0.994
4:53313672:C:G	A367P	0.994
4:53313675:C:G	A366P	0.994
4:53365202:G:T	A247D	0.994
4:53365231:A:C	F237L	0.994
4:53365231:A:T	F237L	0.994
4:53365233:A:G	F237L	0.994
4:53365523:A:G	L140P	0.994
4:52907463:G:C	F612L	0.993
4:52907463:G:T	F612L	0.993
4:52907465:A:G	F612L	0.993
4:53313683:A:C	L363R	0.992
4:53313688:T:A	R361S	0.992

dbSNP variants (sampled 300 via entrez): RS1000012456 (4:53231073 G>A), RS1000017896 (4:52905169 G>A), RS1000020813 (4:53236673 T>A,C), RS1000032656 (4:53263421 T>G), RS1000061590 (4:53023631 G>T), RS1000067688 (4:52941098 T>C), RS1000073773 (4:53066840 C>T), RS1000090407 (4:53073745 G>T), RS1000096474 (4:53301212 T>C), RS1000100654 (4:53115145 T>A), RS1000101493 (4:52900215 G>A,T), RS1000107676 (4:53079759 A>C), RS1000112571 (4:53248013 G>A,C), RS1000128301 (4:53231304 A>C), RS1000134273 (4:53133455 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism, susceptiblity to (MONDO:0020836)

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000659_5	Optic nerve measurement (cup area)	2.000000e-06
GCST001112_3	Lifetime average cigarettes per day in chronic obstructive pulmonary disease	1.000000e-06
GCST004695_2	Insomnia complaints	5.000000e-09
GCST006394_66	Intraocular pressure	3.000000e-08
GCST006462_19	Uterine fibroids	7.000000e-09
GCST006462_20	Uterine fibroids	2.000000e-13
GCST006462_21	Uterine fibroids	3.000000e-09
GCST009545_4	Moderate or severe prolonged lymphopenia in dimethyl fumarate-treated relapsing-remitting multiple sclerosis	3.000000e-06
GCST010699_75	Brain morphology (min-P)	3.000000e-18
GCST010701_71	Cortical surface area (MOSTest)	2.000000e-09
GCST010702_63	Subcortical volume (MOSTest)	8.000000e-12
GCST010703_102	Brain morphology (MOSTest)	6.000000e-21
GCST90002400_426	Plateletcrit	4.000000e-09
GCST90011770_48	Glaucoma (primary open-angle)	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0004346	neuroimaging measurement
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
Benzo(a)pyrene	affects expression, affects methylation, decreases expression	7
Aflatoxin B1	affects expression, decreases expression, decreases methylation	5
trichostatin A	increases expression, affects cotreatment	3
sodium arsenite	increases expression, affects expression, increases abundance	3
Cisplatin	affects cotreatment, decreases expression	3
bisphenol S	affects cotreatment, decreases expression, decreases methylation	2
Acetaminophen	decreases expression	2
Formaldehyde	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
hydroquinone	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
pinostrobin	increases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2ER	Abcam HeLa SCFD2 KO	Cancer cell line	Female
CVCL_TK12	HAP1 SCFD2 (-) 1	Cancer cell line	Male
CVCL_TK13	HAP1 SCFD2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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