NICN1

Summary

NICN1 (nicolin 1, tubulin polyglutamylase complex subunit, HGNC:18317) is a protein-coding gene on chromosome 3p21.31, encoding Nicolin-1 (Q9BSH3).

This protein encoded by this gene localizes to the nucleus and is expressed in numerous tissues including brain, testis, liver, and kidney. This refseq contains genomic sequence in its 3’ UTR which is not supported by experimental evidence. Computer predictions indicate that this region of the 3’ UTR contains hairpin-forming self-complementary sequence which is possibly excised after transcription. This gene has a pseudogene on chromosome X.

Source: NCBI Gene 84276 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 28 total — 2 likely-pathogenic
• MANE Select transcript: NM_032316

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18317
Approved symbol	NICN1
Name	nicolin 1, tubulin polyglutamylase complex subunit
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	MGC12936
Ensembl gene	ENSG00000145029
Ensembl biotype	protein_coding
OMIM	611516
Entrez	84276

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000273598, ENST00000422593, ENST00000423832, ENST00000436744, ENST00000461015, ENST00000494057, ENST00000497742, ENST00000883811, ENST00000883812, ENST00000883813, ENST00000883814

RefSeq mRNA: 1 — MANE Select: NM_032316 NM_032316

CCDS: CCDS2798

Canonical transcript exons

ENST00000273598 — 6 exons

Exon	Start	End
ENSE00000000095	49429108	49429324
ENSE00001228414	49422333	49424874
ENSE00003793926	49425367	49425438
ENSE00003796047	49426252	49426428
ENSE00003797695	49425883	49425996
ENSE00003801068	49424949	49425053

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 92.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1276 / max 100.1655, expressed in 1771 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42264	10.1276	1771

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	92.36	gold quality
superior frontal gyrus	UBERON:0002661	91.30	gold quality
frontal cortex	UBERON:0001870	91.29	gold quality
frontal lobe	UBERON:0016525	91.29	gold quality
right frontal lobe	UBERON:0002810	89.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.84	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.56	gold quality
cerebral cortex	UBERON:0000956	89.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.37	gold quality
cortical plate	UBERON:0005343	89.06	gold quality
cerebellum	UBERON:0002037	89.02	gold quality
cerebellar cortex	UBERON:0002129	88.99	gold quality
cerebellar hemisphere	UBERON:0002245	88.94	gold quality
primary visual cortex	UBERON:0002436	88.60	gold quality
apex of heart	UBERON:0002098	88.53	gold quality
stromal cell of endometrium	CL:0002255	88.31	gold quality
anterior cingulate cortex	UBERON:0009835	88.05	gold quality
right lobe of thyroid gland	UBERON:0001119	87.45	gold quality
left lobe of thyroid gland	UBERON:0001120	87.44	gold quality
brain	UBERON:0000955	87.32	gold quality
thyroid gland	UBERON:0002046	87.32	gold quality
right uterine tube	UBERON:0001302	86.71	gold quality
temporal lobe	UBERON:0001871	86.51	gold quality
amygdala	UBERON:0001876	86.34	gold quality
descending thoracic aorta	UBERON:0002345	86.30	gold quality
nucleus accumbens	UBERON:0001882	86.29	gold quality
fallopian tube	UBERON:0003889	86.18	gold quality
cortex of kidney	UBERON:0001225	86.06	gold quality
right ovary	UBERON:0002118	86.05	gold quality
Ammon’s horn	UBERON:0001954	85.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	14.33
E-ANND-3	no	0.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting NICN1, 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-4673	100.00	66.64	1490
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6081	99.48	66.07	1446

Literature-anchored findings (GeneRIF, showing 1)

• results provide important clues to elucidate the regulation of NPCEDRG gene expression and function (PMID:20821255)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nicn1	ENSDARG00000069677
mus_musculus	Nicn1	ENSMUSG00000032606
rattus_norvegicus	Nicn1	ENSRNOG00000049083

Protein

Protein identifiers

Nicolin-1 — Q9BSH3 (reviewed: Q9BSH3)

Alternative names: NPCEDRG, Tubulin polyglutamylase complex subunit 5

All UniProt accessions (3): Q9BSH3, B2R7Q3, B4DX77

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Part of the neuronal tubulin polyglutamylase complex which contains TPGS1, TPGS2, TTLL1, LRRC49 and NICN1.

Subcellular location. Nucleus.

Tissue specificity. High expression level is found in brain, testis, liver and kidney. Weak expression in spleen, leukocytes, small intestine and colon.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BSH3-1	1	yes
Q9BSH3-2	2

RefSeq proteins (1): NP_115692* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040235	Nicolin-1	Family

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSH3-F1	80.24	0.48

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8955332	Carboxyterminal post-translational modifications of tubulin

MSigDB gene sets: 87 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, WONG_ADULT_TISSUE_STEM_MODULE, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, REACTOME_CARBOXYTERMINAL_POST_TRANSLATIONAL_MODIFICATIONS_OF_TUBULIN, chr3p21, GOCC_SUPRAMOLECULAR_POLYMER, ARID5B_TARGET_GENES, CIITA_TARGET_GENES, ELF2_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (3): nucleoplasm (GO:0005654), microtubule (GO:0005874), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
nuclear lumen	1
cellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

407 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NICN1	NONO	P30807	619
NICN1	TMEM178A	Q8NBL3	613
NICN1	LRRC49	Q8IUZ0	589
NICN1	FTSJ3	Q8IY81	518
NICN1	TTLL1	O95922	483
NICN1	ZNF304	Q9HCX3	463
NICN1	IFIH1	Q9BYX4	437
NICN1	INTS2	Q9H0H0	429
NICN1	DESI1	Q6ICB0	415
NICN1	SUGP1	Q8IWZ8	411
NICN1	BPNT1	O95861	404
NICN1	SCAPER	Q9BY12	389
NICN1	TPGS2	Q68CL5	388
NICN1	TPGS1	Q6ZTW0	381
NICN1	DESI2	Q9BSY9	379

IntAct

38 interactions, top by confidence:

A	B	Type	Score
NICN1	TTLL1	psi-mi:“MI:0914”(association)	0.640
NICN1	TPGS2	psi-mi:“MI:0914”(association)	0.640
ATP6V0D2	NICN1	psi-mi:“MI:0915”(physical association)	0.560
ZNF77	NICN1	psi-mi:“MI:0915”(physical association)	0.560
NFKBID	NICN1	psi-mi:“MI:0915”(physical association)	0.560
TTC9C	NICN1	psi-mi:“MI:0915”(physical association)	0.560
TLX3	NICN1	psi-mi:“MI:0915”(physical association)	0.560
TENT5B	NICN1	psi-mi:“MI:0915”(physical association)	0.560
P4HA3	NICN1	psi-mi:“MI:0915”(physical association)	0.560
NICN1	RUSC1	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC2	NICN1	psi-mi:“MI:0915”(physical association)	0.560
POGZ	NICN1	psi-mi:“MI:0915”(physical association)	0.560
CSTPP1	TPGS2	psi-mi:“MI:0914”(association)	0.530
TTLL1	CAMK2B	psi-mi:“MI:0914”(association)	0.350
NICN1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TTLL1	RGS12	psi-mi:“MI:0914”(association)	0.350
ZNF77	NICN1	psi-mi:“MI:0915”(physical association)	0.000
NFKBID	NICN1	psi-mi:“MI:0915”(physical association)	0.000
P4HA3	NICN1	psi-mi:“MI:0915”(physical association)	0.000
RUSC1	NICN1	psi-mi:“MI:0915”(physical association)	0.000
TRAPPC2	NICN1	psi-mi:“MI:0915”(physical association)	0.000
TTC9C	NICN1	psi-mi:“MI:0915”(physical association)	0.000
TLX3	NICN1	psi-mi:“MI:0915”(physical association)	0.000
TENT5B	NICN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (47): NICN1 (Affinity Capture-MS), C11orf49 (Affinity Capture-MS), LRRC49 (Affinity Capture-MS), TTLL1 (Affinity Capture-MS), TPGS1 (Affinity Capture-MS), TPGS2 (Affinity Capture-MS), KIAA1841 (Affinity Capture-MS), TBC1D19 (Affinity Capture-MS), SMG8 (Affinity Capture-MS), UBB (Affinity Capture-MS), NICN1 (Proximity Label-MS), NICN1 (Two-hybrid), ATP6V0D2 (Two-hybrid), P4HA3 (Two-hybrid), FAM46B (Two-hybrid)

ESM2 similar proteins: A1A4J7, A2CEI4, A2RV06, B2RYI0, E7F654, E7FAW3, E9QAM5, F1Q7Z7, F1QNV4, O01939, O75064, O75153, O95248, P97564, Q08CY4, Q0P4Q0, Q0VA04, Q1L908, Q1LXZ7, Q2YDW2, Q32PH0, Q3T1I9, Q3U1Y4, Q4JF28, Q5U249, Q61586, Q6GPP1, Q6PD24, Q6TEN6, Q6ZNJ1, Q6ZPE2, Q6ZPG2, Q6ZQA0, Q6ZTN6, Q764M6, Q7T006, Q7TMQ7, Q7ZVS8, Q80U56, Q861Y6

Diamond homologs: Q861Y6, Q9BSH3, Q9CQM0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NICN1	“form complex”	“Tubulin polyglutamylase complex”	binding

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	2
Uncertain significance	17
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1323888	NM_000481.4(AMT):c.3G>A (p.Met1Ile)	Likely pathogenic
965232	NC_000003.12:g.49422370_49422479del	Likely pathogenic

SpliceAI

1190 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49422437:A:AC	donor_gain	1.0000
3:49422437:ACAG:A	donor_gain	1.0000
3:49422437:ACAGC:A	donor_gain	1.0000
3:49422438:C:CC	donor_gain	1.0000
3:49422438:CAG:C	donor_gain	1.0000
3:49422438:CAGC:C	donor_gain	1.0000
3:49422438:CAGCC:C	donor_gain	1.0000
3:49424947:A:AC	donor_gain	1.0000
3:49424948:C:CC	donor_gain	1.0000
3:49424948:CAT:C	donor_gain	1.0000
3:49425052:CC:C	acceptor_gain	1.0000
3:49425053:CC:C	acceptor_gain	1.0000
3:49425880:TACCT:T	donor_loss	1.0000
3:49425881:A:AC	donor_gain	1.0000
3:49425881:ACC:A	donor_loss	1.0000
3:49425882:C:CC	donor_gain	1.0000
3:49426275:A:AC	donor_gain	1.0000
3:49426275:ACT:A	donor_gain	1.0000
3:49426276:C:CC	donor_gain	1.0000
3:49426276:CTC:C	donor_gain	1.0000
3:49426873:CAGT:C	donor_gain	1.0000
3:49429104:TCACC:T	donor_loss	1.0000
3:49429105:CACCT:C	donor_loss	1.0000
3:49429106:A:AC	donor_gain	1.0000
3:49429106:A:AG	donor_loss	1.0000
3:49429107:C:CC	donor_gain	1.0000
3:49429107:CCT:C	donor_gain	1.0000
3:49429107:CCTC:C	donor_loss	1.0000
3:49424943:A:AC	donor_gain	0.9900
3:49424943:ACTT:A	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000354759 (3:49429497 A>G), RS1000947311 (3:49424651 A>G), RS1001144470 (3:49422591 A>T), RS1001207998 (3:49426546 G>A,T), RS1001443033 (3:49426070 G>A,T), RS1001735262 (3:49425023 C>G,T), RS1001774580 (3:49425507 C>T), RS1002078582 (3:49423496 C>T), RS1002293411 (3:49430803 C>T), RS1002403564 (3:49424230 A>G), RS1002436030 (3:49424546 G>A), RS1002668745 (3:49430615 T>C), RS1005101369 (3:49425746 C>T), RS1005591446 (3:49424531 A>G), RS1005595672 (3:49430832 C>T)

Disease associations

OMIM: gene MIM:611516 | disease phenotypes: MIM:605899, MIM:620398

GenCC curated gene-disease

Mondo (3): glycine encephalopathy (MONDO:0011612), glycine encephalopathy 2 (MONDO:0958192), glycine encephalopathy 1 (MONDO:0958179)

Orphanet (1): Glycine encephalopathy (Orphanet:407)

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST002774_6	Cognitive function	8.000000e-06
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST005316_112	Intelligence (MTAG)	9.000000e-13
GCST005316_128	Intelligence (MTAG)	3.000000e-11
GCST006269_320	General cognitive ability	1.000000e-11
GCST006269_499	General cognitive ability	2.000000e-19
GCST006804_182	Red cell distribution width	2.000000e-08
GCST006922_9	Regular attendance at a religious group	3.000000e-08
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST008357_20	Mood instability	4.000000e-11
GCST008849_2	Depressive symptoms (binary sum-score)	7.000000e-09
GCST010002_422	Refractive error	4.000000e-14
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0009188	Red cell distribution width
EFO:0009592	social interaction measurement
EFO:0008475	mood instability measurement
EFO:0007006	depressive symptom measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression, affects cotreatment	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	increases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan