SYNDIG1L

Summary

SYNDIG1L (synapse differentiation inducing 1 like, HGNC:32388) is a protein-coding gene on chromosome 14q24.3, encoding Synapse differentiation-inducing gene protein 1-like (A6NDD5).

Predicted to be located in Golgi apparatus. Predicted to be active in intracellular membrane-bounded organelle and membrane.

Source: NCBI Gene 646658 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_001105579

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32388
Approved symbol	SYNDIG1L
Name	synapse differentiation inducing 1 like
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	capucin, IFITMD4, DSPC1, SynDIG2
Ensembl gene	ENSG00000183379
Ensembl biotype	protein_coding
OMIM	609999
Entrez	646658

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000331628, ENST00000554823, ENST00000554953, ENST00000896719, ENST00000896720, ENST00000912482, ENST00000971959

RefSeq mRNA: 1 — MANE Select: NM_001105579 NM_001105579

CCDS: CCDS41970

Canonical transcript exons

ENST00000331628 — 4 exons

Exon	Start	End
ENSE00001320434	74405899	74407693
ENSE00001330790	74409328	74409801
ENSE00003850145	74425912	74426210
ENSE00003890711	74407849	74407989

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 99.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0839 / max 276.4622, expressed in 62 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144019	0.7571	52
144023	0.2725	29
144024	0.0234	12
144021	0.0154	11
144022	0.0103	7
144020	0.0052	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
putamen	UBERON:0001874	99.30	gold quality
caudate nucleus	UBERON:0001873	98.90	gold quality
nucleus accumbens	UBERON:0001882	98.23	gold quality
lateral globus pallidus	UBERON:0002476	96.68	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.61	gold quality
substantia nigra	UBERON:0002038	81.68	gold quality
pancreatic ductal cell	CL:0002079	81.50	silver quality
globus pallidus	UBERON:0001875	80.24	gold quality
hypothalamus	UBERON:0001898	79.90	gold quality
midbrain	UBERON:0001891	79.62	gold quality
medial globus pallidus	UBERON:0002477	77.94	gold quality
dorsal plus ventral thalamus	UBERON:0001897	75.79	gold quality
endothelial cell	CL:0000115	72.16	gold quality
forebrain	UBERON:0001890	70.90	gold quality
epithelial cell of pancreas	CL:0000083	70.10	gold quality
prefrontal cortex	UBERON:0000451	69.33	gold quality
cauda epididymis	UBERON:0004360	69.29	gold quality
brain	UBERON:0000955	68.93	gold quality
anterior cingulate cortex	UBERON:0009835	68.68	gold quality
ventral tegmental area	UBERON:0002691	68.63	gold quality
kidney epithelium	UBERON:0004819	68.58	gold quality
substantia nigra pars reticulata	UBERON:0001966	68.05	gold quality
amygdala	UBERON:0001876	67.64	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	67.16	gold quality
spinal cord	UBERON:0002240	66.31	gold quality
cardiac muscle of right atrium	UBERON:0003379	66.21	gold quality
left ventricle myocardium	UBERON:0006566	65.59	gold quality
corpus epididymis	UBERON:0004359	65.46	silver quality
frontal cortex	UBERON:0001870	65.11	gold quality
neocortex	UBERON:0001950	65.05	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

90 targeting SYNDIG1L, 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-4673	100.00	66.64	1490
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-516A-3P	99.46	67.96	1378

Literature-anchored findings (GeneRIF, showing 1)

• Cloning and characterization of the TMEM90A (capucin) ortholog in mouse. (PMID:16359841)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	syndig1l	ENSDARG00000042390
mus_musculus	Syndig1l	ENSMUSG00000071234
rattus_norvegicus	Syndig1l	ENSRNOG00000027645

Paralogs (3): SYNDIG1 (ENSG00000101463), TMEM91 (ENSG00000142046), PMIS2 (ENSG00000283758)

Protein

Protein identifiers

Synapse differentiation-inducing gene protein 1-like — A6NDD5 (reviewed: A6NDD5)

Alternative names: Capucin, Dispanin subfamily C member 1, Transmembrane protein 90A

All UniProt accessions (2): A6NDD5, G3V402

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane. Golgi apparatus. cis-Golgi network.

Similarity. Belongs to the CD225/Dispanin family.

RefSeq proteins (1): NP_001099049* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007593	CD225/Dispanin_fam	Family

Pfam: PF04505

UniProt features (10 total): topological domain 3, region of interest 3, transmembrane region 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NDD5-F1	55.22	0.01

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 44 (showing top): chr14q24, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, ZNF664_TARGET_GENES, GSE10094_LCMV_VS_LISTERIA_IND_EFF_CD4_TCELL_DN, MIR548AR_3P, MIR548F_3P, MIR548BC, MIR548AZ_3P, MIR548A_3P, MIR548E_3P, MIR6825_5P, MIR4492, MIR6721_5P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYNDIG1L	VRTN	Q9H8Y1	704
SYNDIG1L	GSG1L2	A8MUP6	643
SYNDIG1L	TMEM233	B4DJY2	594
SYNDIG1L	PROX2	Q3B8N5	542
SYNDIG1L	ANKRD13B	Q86YJ7	532
SYNDIG1L	PRRT1B	A0A1B0GWB2	509
SYNDIG1L	PGGHG	Q32M88	497
SYNDIG1L	TMEM108	Q6UXF1	489
SYNDIG1L	AREL1	O15033	475
SYNDIG1L	PMIS2	A0A1W2PS18	471
SYNDIG1L	SYT6	Q5T7P8	470
SYNDIG1L	DNAJC30	Q96LL9	468
SYNDIG1L	TRARG1	Q8IXB3	456
SYNDIG1L	LARP1B	Q659C4	454
SYNDIG1L	STMND1	H3BQB6	447

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GU29, A2A9F4, A2ANU3, A4IFJ1, A6NDD5, A6NMD0, M3WHG5, O75298, Q08DM6, Q32M26, Q3USQ7, Q4R532, Q58DZ9, Q5BK39, Q63247, Q64322, Q68DV7, Q6AY88, Q6KAU7, Q6NUJ2, Q6ZNR0, Q76N89, Q76NI1, Q8BLR5, Q8BP99, Q8BR26, Q8BWG4, Q8BZW2, Q8C581, Q8C708, Q8IUC6, Q8IXW0, Q8K0W3, Q8NAX2, Q8NC06, Q8NDX1, Q8R2H3, Q8VIM4, Q8WV48, Q8WWG9

Diamond homologs: A2ANU3, A4IFJ1, A6NDD5, O35449, Q08DM6, Q3USQ7, Q4R532, Q58DZ9, Q5TZE2, Q6MG82, Q6ZNR0, Q8C581, Q99946, Q9H7V2, A0A1B0GWB2, Q6DFT4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

643 predictions. Top by Δscore:

Variant	Effect	Δscore
14:74407694:C:CC	acceptor_gain	1.0000
14:74407843:TCTTA:T	donor_loss	1.0000
14:74407844:CTTA:C	donor_loss	1.0000
14:74407845:TTAC:T	donor_loss	1.0000
14:74407847:A:AG	donor_loss	1.0000
14:74407847:AC:A	donor_gain	1.0000
14:74407847:ACC:A	donor_gain	1.0000
14:74407847:ACCC:A	donor_gain	1.0000
14:74407848:CC:C	donor_gain	1.0000
14:74407848:CCC:C	donor_gain	1.0000
14:74407848:CCCC:C	donor_gain	1.0000
14:74407850:C:CA	donor_gain	1.0000
14:74407985:TCGCT:T	acceptor_gain	1.0000
14:74407986:CGCT:C	acceptor_gain	1.0000
14:74407986:CGCTC:C	acceptor_gain	1.0000
14:74407988:CT:C	acceptor_gain	1.0000
14:74407990:C:CC	acceptor_gain	1.0000
14:74409323:CTCA:C	donor_loss	1.0000
14:74409326:A:AC	donor_gain	1.0000
14:74409326:ACCT:A	donor_gain	1.0000
14:74409327:C:CC	donor_gain	1.0000
14:74409327:CCT:C	donor_gain	1.0000
14:74409327:CCTC:C	donor_gain	1.0000
14:74425906:CCTTA:C	donor_loss	1.0000
14:74425907:CTTA:C	donor_loss	1.0000
14:74425908:TTAC:T	donor_loss	1.0000
14:74425909:TACCT:T	donor_loss	1.0000
14:74425910:A:AT	donor_loss	1.0000
14:74407689:CTGGT:C	acceptor_gain	0.9900
14:74407842:CTCTT:C	donor_loss	0.9900

AlphaMissense

1538 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:74407887:A:G	W174R	0.998
14:74407887:A:T	W174R	0.998
14:74407896:A:G	C171R	0.996
14:74407871:G:T	A179D	0.995
14:74407883:G:T	P175Q	0.994
14:74407893:A:G	C172R	0.994
14:74407603:C:G	G217R	0.993
14:74407603:C:T	G217R	0.993
14:74407883:G:C	P175R	0.993
14:74407877:C:T	G177D	0.992
14:74407878:C:G	G177R	0.992
14:74407597:C:G	G219R	0.991
14:74407868:G:T	A180D	0.991
14:74407656:G:T	A199D	0.990
14:74407891:G:C	C172W	0.990
14:74407602:C:T	G217E	0.989
14:74407644:G:A	S203F	0.989
14:74407892:C:T	C172Y	0.989
14:74407898:A:T	L170H	0.989
14:74407596:C:T	G219D	0.987
14:74407884:G:A	P175S	0.985
14:74407888:G:C	F173L	0.985
14:74407888:G:T	F173L	0.985
14:74407890:A:G	F173L	0.985
14:74407603:C:A	G217W	0.983
14:74407901:A:T	M169K	0.983
14:74407901:A:C	M169R	0.982
14:74407608:G:T	A215D	0.980
14:74407869:C:G	A180P	0.980
14:74407874:A:T	I178N	0.980

dbSNP variants (sampled 300 via entrez): RS1000013296 (14:74446593 A>G), RS1000065059 (14:74456775 A>C), RS1000150401 (14:74458848 T>C), RS1000182617 (14:74410960 A>G), RS1000272561 (14:74475812 CCGCCCT>C), RS1000286358 (14:74432153 G>GTGTC), RS1000289471 (14:74415021 A>C,G), RS1000294701 (14:74444218 C>A,T), RS1000327462 (14:74420878 C>T), RS1000354041 (14:74416699 A>G,T), RS1000381300 (14:74420551 G>A,T), RS1000393252 (14:74439521 T>G), RS1000395064 (14:74462045 C>A), RS1000432362 (14:74465378 C>T), RS1000479138 (14:74451788 G>A,C)

Disease associations

OMIM: gene MIM:609999 | disease phenotypes: MIM:257220

GenCC curated gene-disease

Mondo (1): Niemann-Pick disease, type C1 (MONDO:0009757)

Orphanet (1): Niemann-Pick disease type C (Orphanet:646)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs140130028	NPC2, SYNDIG1L		0.00	0

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	2
methyleugenol	decreases expression	1
licochalcone B	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Cadmium Chloride	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04860960	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Study to Evaluate Intravenous Trappsol(R) Cyclo(TM) in Pediatric and Adult Patients With Niemann-Pick Disease Type C1
NCT01747135	PHASE1	COMPLETED	Hydroxypropyl Beta Cyclodextrin for Niemann-Pick Type C1 Disease
NCT02939547	PHASE1	COMPLETED	Study of the Pharmacokinetics of Trappsol and Effects on Potential Biomarkers of Niemann-Pick C1 (NPC1)
NCT03893071	PHASE1	UNKNOWN	Open-Label Study of Long-Term Safety and Efficacy of Intravenous Trappsol Cyclo (HPβCD) in Niemann-Pick Disease Type C
NCT02912793	PHASE1/PHASE2	COMPLETED	Safety and Efficacy of Intravenous Trappsol Cyclo (HPBCD) in Niemann-Pick Type C Patients
NCT03887533	PHASE1/PHASE2	TERMINATED	Combined Intrathecal and Intravenous VTS-270 Therapy for Liver and Neurological Disease Associated With Niemann-Pick Disease, Type C1
NCT03201627	EARLY_PHASE1	UNKNOWN	Study of Lithium Carbonate to Treat Niemann-Pick Type C1 Disease
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05642221	Not specified	COMPLETED	Functional Near-Infrared Spectroscopy (fNIRS) Combined With Diffuse Correlation Spectroscopy (DCS) in Neurocognitive Disease as Compared to Healthy Neurotypical Controls