ICA1L

Summary

ICA1L (islet cell autoantigen 1 like, HGNC:14442) is a protein-coding gene on chromosome 2q33.2, encoding Islet cell autoantigen 1-like protein (Q8NDH6).

Predicted to enable protein domain specific binding activity. Predicted to be involved in regulation of transport. Predicted to act upstream of or within spermatid development. Predicted to be located in acrosomal vesicle. Predicted to be active in Golgi apparatus.

Source: NCBI Gene 130026 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_001288622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14442
Approved symbol	ICA1L
Name	islet cell autoantigen 1 like
Location	2q33.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163596
Ensembl biotype	protein_coding
OMIM	621083
Entrez	130026

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 38 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000358299, ENST00000392237, ENST00000411681, ENST00000412210, ENST00000416760, ENST00000418208, ENST00000419460, ENST00000420558, ENST00000421334, ENST00000425178, ENST00000432273, ENST00000435143, ENST00000437978, ENST00000438804, ENST00000441547, ENST00000450143, ENST00000454326, ENST00000457524, ENST00000476602, ENST00000484561, ENST00000494560, ENST00000617388, ENST00000909901, ENST00000909904, ENST00000909905, ENST00000909906, ENST00000909907, ENST00000909908, ENST00000909909, ENST00000931778, ENST00000942325, ENST00000942326, ENST00000942327, ENST00000942328, ENST00000942329, ENST00000942330, ENST00000942331, ENST00000942332, ENST00000942333, ENST00000942334, ENST00000942335, ENST00000942336, ENST00000942337

RefSeq mRNA: 4 — MANE Select: NM_001288622 NM_001288622, NM_001288623, NM_001288624, NM_138468

CCDS: CCDS2354, CCDS74632

Canonical transcript exons

ENST00000358299 — 13 exons

Exon	Start	End
ENSE00001511201	202871619	202871766
ENSE00001621591	202773176	202779648
ENSE00001635805	202796890	202796964
ENSE00001640228	202788830	202789087
ENSE00001667988	202814702	202814784
ENSE00001684511	202811746	202811789
ENSE00002185524	202819701	202819899
ENSE00003475594	202828848	202829016
ENSE00003567645	202815911	202816009
ENSE00003589336	202785918	202786007
ENSE00003667806	202817418	202817543
ENSE00003786241	202825695	202825767
ENSE00003790694	202821358	202821481

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 96.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.4860 / max 131.8974, expressed in 988 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33285	1.3254	460
33286	1.0574	388
33289	0.4979	255
33287	0.1671	84
33288	0.1627	78
33284	0.1043	50
33282	0.0752	25
33283	0.0566	17
33281	0.0394	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	96.41	gold quality
bronchus	UBERON:0002185	95.57	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.57	gold quality
cortical plate	UBERON:0005343	93.42	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.11	gold quality
endothelial cell	CL:0000115	92.05	gold quality
primary visual cortex	UBERON:0002436	91.50	gold quality
corpus callosum	UBERON:0002336	91.40	gold quality
cerebellum	UBERON:0002037	91.27	gold quality
cerebellar cortex	UBERON:0002129	91.17	gold quality
cerebellar hemisphere	UBERON:0002245	91.12	gold quality
occipital lobe	UBERON:0002021	90.94	gold quality
substantia nigra pars compacta	UBERON:0001965	90.87	gold quality
middle temporal gyrus	UBERON:0002771	90.79	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.79	gold quality
mucosa of stomach	UBERON:0001199	90.56	gold quality
lateral globus pallidus	UBERON:0002476	90.55	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.71	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.70	gold quality
right uterine tube	UBERON:0001302	89.51	gold quality
oviduct epithelium	UBERON:0004804	89.46	gold quality
superior frontal gyrus	UBERON:0002661	89.28	gold quality
pituitary gland	UBERON:0000007	89.17	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.12	gold quality
cerebellar vermis	UBERON:0004720	89.09	gold quality
adenohypophysis	UBERON:0002196	88.41	gold quality
oocyte	CL:0000023	88.35	gold quality
ventricular zone	UBERON:0003053	88.28	gold quality
calcaneal tendon	UBERON:0003701	88.10	gold quality
entorhinal cortex	UBERON:0002728	88.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

221 targeting ICA1L, 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-4682	100.00	68.89	1258
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 1)

• ICA1L Is Associated with Small Vessel Disease: A Proteome-Wide Association Study in Small Vessel Stroke and Intracerebral Haemorrhage. (PMID:35328582)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ical1	ENSDARG00000057688
mus_musculus	Ica1l	ENSMUSG00000026018
rattus_norvegicus	Ica1l	ENSRNOG00000017258
drosophila_melanogaster	ICA69	FBGN0037050
caenorhabditis_elegans	ric-19	WBGENE00004368

Paralogs (1): ICA1 (ENSG00000003147)

Protein

Protein identifiers

Islet cell autoantigen 1-like protein — Q8NDH6 (reviewed: Q8NDH6)

Alternative names: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 14 protein, Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 15 protein

All UniProt accessions (14): C9J0T2, C9J101, C9J1M7, C9J5Z0, C9J9Z8, C9JAQ4, C9JDK6, C9JDM8, C9JEN4, Q8NDH6, C9JEP0, C9JP49, C9JRB6, F8WBQ1

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NDH6-1	1	yes
Q8NDH6-2	2

RefSeq proteins (4): NP_001275551, NP_001275552, NP_001275553, NP_612477 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006723	Islet_autoAg_Ica1_C	Domain
IPR010504	AH_dom	Domain
IPR024114	Islet_autoAg_Ica1/Ica1-like	Family
IPR027267	AH/BAR_dom_sf	Homologous_superfamily

Pfam: PF04629, PF06456

UniProt features (10 total): sequence conflict 3, region of interest 2, compositionally biased region 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NDH6-F1	68.89	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 111 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOCC_SECRETORY_GRANULE, GOZGIT_ESR1_TARGETS_DN, GOBP_MALE_GAMETE_GENERATION, WANG_LMO4_TARGETS_DN, GOBP_SECRETION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MEMBRANE_ORGANIZATION, GOBP_REGULATION_OF_TRANSPORT, GOCC_SECRETORY_VESICLE, GOCC_SECRETORY_GRANULE_MEMBRANE, GOCC_ACROSOMAL_VESICLE, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP

GO Biological Process (3): spermatid development (GO:0007286), regulation of secretion (GO:0051046), membrane bending (GO:0097753)

GO Molecular Function (3): protein domain specific binding (GO:0019904), membrane curvature sensor activity (GO:0140090), protein binding (GO:0005515)

GO Cellular Component (4): acrosomal vesicle (GO:0001669), secretory granule membrane (GO:0030667), cytoplasm (GO:0005737), endomembrane system (GO:0012505)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
secretory granule	2
cellular anatomical structure	2
germ cell development	1
spermatid differentiation	1
secretion	1
regulation of transport	1
membrane organization	1
protein binding	1
lipid binding	1
molecular sensor activity	1
binding	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ICA1L	NBEAL1	Q6ZS30	693
ICA1L	FAM117B	Q6P1L5	654
ICA1L	PICK1	Q9NRD5	636
ICA1L	WDR12	Q9GZL7	571
ICA1L	RTF2	Q9BY42	561
ICA1L	SNX32	Q86XE0	551
ICA1L	CYP20A1	Q6UW02	544
ICA1L	GK5	Q6ZS86	544
ICA1L	ZCCHC14	Q8WYQ9	506
ICA1L	ZNF429	Q86V71	498
ICA1L	TOM1L2	Q6ZVM7	467
ICA1L	C14orf119	Q9NWQ9	461
ICA1L	ZNF714	Q96N38	450
ICA1L	SLC25A44	Q96H78	447
ICA1L	CYB5D2	Q8WUJ1	445

IntAct

12 interactions, top by confidence:

A	B	Type	Score
ICA1L	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
KIFC3	ICA1L	psi-mi:“MI:0915”(physical association)	0.560
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
PICK1	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
GFAP	ICA1L	psi-mi:“MI:0915”(physical association)	0.400
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): ICA1L (Two-hybrid), ICA1L (Affinity Capture-MS), ICA1L (Affinity Capture-MS), ICA1L (Affinity Capture-RNA), ICA1L (Protein-RNA), ICA1L (Synthetic Lethality), ICA1L (Two-hybrid), ICA1L (Two-hybrid), ICA1L (Two-hybrid), ICA1L (Two-hybrid), KRT27 (Two-hybrid), GCC1 (Two-hybrid), HGS (Two-hybrid), ICA1L (Affinity Capture-MS), ICA1L (Protein-peptide)

ESM2 similar proteins: A9ZLX4, B5DF41, D3Z6Q9, D3ZFJ3, F1LQX4, O00499, O08539, O08839, O15079, O75151, P49140, P59672, P78524, P97411, Q05084, Q13191, Q13905, Q14432, Q17R89, Q3B7M3, Q3TTA7, Q3TY65, Q3YEC7, Q5SSM3, Q5U2T3, Q5U3K5, Q5ZKL7, Q62739, Q62865, Q63054, Q68EM7, Q68FR2, Q6DFR2, Q6GQL0, Q6RUG5, Q80U23, Q86XL3, Q86XZ4, Q8K1N4, Q8K4S7

Diamond homologs: P91124, P97411, Q05084, Q3TY65, Q63054, Q6RUG5, Q8NDH6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2580 predictions. Top by Δscore:

Variant	Effect	Δscore
2:202785917:CAT:C	donor_gain	1.0000
2:202785917:CATCT:C	donor_gain	1.0000
2:202786003:CCAGT:C	acceptor_gain	1.0000
2:202786004:CAGT:C	acceptor_gain	1.0000
2:202786004:CAGTC:C	acceptor_gain	1.0000
2:202789095:G:GC	acceptor_gain	1.0000
2:202796965:C:CC	acceptor_gain	1.0000
2:202796980:A:C	acceptor_gain	1.0000
2:202814690:ATG:A	donor_gain	1.0000
2:202814700:A:AC	donor_gain	1.0000
2:202814701:C:CC	donor_gain	1.0000
2:202814704:A:AC	donor_gain	1.0000
2:202816008:CT:C	acceptor_gain	1.0000
2:202816010:C:CC	acceptor_gain	1.0000
2:202819699:A:AC	donor_gain	1.0000
2:202819700:C:CC	donor_gain	1.0000
2:202819700:CTTTT:C	donor_gain	1.0000
2:202819709:A:C	donor_gain	1.0000
2:202819714:T:A	donor_gain	1.0000
2:202819895:CCAAT:C	acceptor_gain	1.0000
2:202819896:CAAT:C	acceptor_gain	1.0000
2:202819896:CAATC:C	acceptor_gain	1.0000
2:202819900:C:CC	acceptor_gain	1.0000
2:202819900:C:CG	acceptor_loss	1.0000
2:202779529:T:TA	donor_gain	0.9900
2:202779649:C:CC	acceptor_gain	0.9900
2:202779652:T:TC	acceptor_gain	0.9900
2:202785916:A:AC	donor_gain	0.9900
2:202785916:ACAT:A	donor_gain	0.9900
2:202785917:C:CC	donor_gain	0.9900

AlphaMissense

3211 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:202819792:C:G	R156P	0.995
2:202819707:A:C	F184L	0.992
2:202819707:A:T	F184L	0.992
2:202819709:A:G	F184L	0.992
2:202819762:A:G	M166T	0.992
2:202819771:A:G	L163P	0.992
2:202779616:A:G	W456R	0.991
2:202779616:A:T	W456R	0.991
2:202819848:G:C	F137L	0.991
2:202819848:G:T	F137L	0.991
2:202819850:A:G	F137L	0.991
2:202819784:A:C	Y159D	0.990
2:202817431:A:G	L224P	0.988
2:202819793:G:T	R156S	0.988
2:202817457:A:C	S215R	0.987
2:202817457:A:T	S215R	0.987
2:202817459:T:G	S215R	0.987
2:202819766:A:G	W165R	0.987
2:202819766:A:T	W165R	0.987
2:202819779:T:A	R160S	0.987
2:202819779:T:G	R160S	0.987
2:202819783:T:G	Y159S	0.986
2:202819784:A:G	Y159H	0.986
2:202817455:C:G	R216P	0.985
2:202819708:A:G	F184S	0.985
2:202819780:C:G	R160T	0.984
2:202819870:A:G	L130P	0.984
2:202817479:T:A	K208I	0.983
2:202828871:C:G	A47P	0.983
2:202817488:A:T	V205D	0.982

dbSNP variants (sampled 300 via entrez): RS1000024739 (2:202827120 G>A), RS1000069047 (2:202854890 G>T), RS1000069672 (2:202807158 G>A), RS1000082519 (2:202834167 T>A), RS1000085303 (2:202848333 A>C), RS1000138245 (2:202799346 T>G), RS1000143642 (2:202808772 C>A,T), RS1000218896 (2:202798111 T>C), RS1000226529 (2:202813499 G>T), RS1000237141 (2:202841333 G>A), RS1000303816 (2:202867599 A>G), RS1000328405 (2:202841370 G>A,C), RS1000335394 (2:202820762 C>G), RS1000343598 (2:202774031 C>T), RS1000442231 (2:202813123 A>G)

Disease associations

OMIM: gene MIM:621083 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST006288_242	Heel bone mineral density	5.000000e-06
GCST006288_505	Heel bone mineral density	6.000000e-11
GCST006586_5	Urinary albumin excretion	1.000000e-11
GCST008790_11	Urinary albumin-to-creatinine ratio	3.000000e-14
GCST008791_28	Microalbuminuria	4.000000e-06
GCST008794_25	Urinary albumin-to-creatinine ratio	3.000000e-14
GCST008876_34	Non-lobar intracerebral hemorrhage (MTAG)	2.000000e-08
GCST009640_12	Urinary albumin-to-creatinine ratio	2.000000e-12
GCST010101_5	White matter hyperintensities	4.000000e-13
GCST010102_1	White matter integrity (fractional anisotropy)	7.000000e-08
GCST010102_2	White matter integrity (fractional anisotropy)	6.000000e-09
GCST010698_18	Subcortical volume (min-P)	1.000000e-08
GCST010699_69	Brain morphology (min-P)	9.000000e-20
GCST010700_6	Cortical thickness (MOSTest)	2.000000e-14
GCST010701_36	Cortical surface area (MOSTest)	2.000000e-24
GCST010702_146	Subcortical volume (MOSTest)	2.000000e-13
GCST010703_42	Brain morphology (MOSTest)	1.000000e-08
GCST90000582_9	Spontaneous coronary artery dissection	6.000000e-06
GCST90002395_353	Mean platelet volume	3.000000e-14
GCST90002402_286	Platelet count	2.000000e-16
GCST90014122_1	Lacunar stroke	4.000000e-09
GCST90014123_1	Lacunar stroke	5.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004285	albuminuria
EFO:0007778	urinary albumin to creatinine ratio
EFO:0010178	non-lobar intracerebral hemorrhage
EFO:0005665	white matter hyperintensity measurement
EFO:0004641	white matter integrity
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression, affects cotreatment	3
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	2
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
pentanal	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Hydrogen Peroxide	affects expression	1
Lead	decreases expression	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
1-Butanol	affects cotreatment, decreases expression, increases abundance	1
p-Chloromercuribenzoic Acid	increases expression	1

Clinical trials (associated diseases)

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