CYRIA

Summary

CYRIA (CYFIP related Rac1 interactor A, HGNC:25373) is a protein-coding gene on chromosome 2p24.2, encoding CYFIP-related Rac1 interactor A (Q9H0Q0). May negatively regulate RAC1 signaling and RAC1-driven cytoskeletal remodeling.

Predicted to enable small GTPase binding activity. Predicted to be involved in regulation of actin filament polymerization. Predicted to be located in membrane.

Source: NCBI Gene 81553 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 39 total — 3 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_030797

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25373
Approved symbol	CYRIA
Name	CYFIP related Rac1 interactor A
Location	2p24.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP566A1524, FLJ11080, CYRI-A
Ensembl gene	ENSG00000197872
Ensembl biotype	protein_coding
Entrez	81553

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 26 protein_coding, 1 retained_intron

ENST00000381323, ENST00000406434, ENST00000445605, ENST00000451689, ENST00000469507, ENST00000871551, ENST00000871552, ENST00000871553, ENST00000871554, ENST00000871555, ENST00000871556, ENST00000871557, ENST00000871558, ENST00000871559, ENST00000871560, ENST00000871561, ENST00000871562, ENST00000871563, ENST00000871564, ENST00000935274, ENST00000935275, ENST00000935276, ENST00000966326, ENST00000966327, ENST00000966328, ENST00000966329, ENST00000966330

RefSeq mRNA: 1 — MANE Select: NM_030797 NM_030797

CCDS: CCDS1688

Canonical transcript exons

ENST00000381323 — 12 exons

Exon	Start	End
ENSE00001162795	16555069	16555139
ENSE00001162802	16559460	16559586
ENSE00001162817	16561456	16561533
ENSE00001162821	16562005	16562141
ENSE00001162824	16563989	16564094
ENSE00001162830	16565646	16565767
ENSE00001166443	16588050	16588129
ENSE00001488178	16549459	16552999
ENSE00001488213	16623864	16624019
ENSE00001488214	16665780	16665834
ENSE00001607999	16560990	16561069
ENSE00003515999	16561161	16561277

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 99.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7528 / max 1026.4636, expressed in 1340 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27024	16.3248	1248
27025	2.6988	800
27023	0.5648	165
27017	0.1234	52
27018	0.0221	10
27016	0.0189	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.50	gold quality
monocyte	CL:0000576	94.81	gold quality
mononuclear cell	CL:0000842	94.68	gold quality
middle temporal gyrus	UBERON:0002771	94.57	gold quality
leukocyte	CL:0000738	94.49	gold quality
superior frontal gyrus	UBERON:0002661	94.20	gold quality
prefrontal cortex	UBERON:0000451	94.15	gold quality
entorhinal cortex	UBERON:0002728	93.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.49	gold quality
orbitofrontal cortex	UBERON:0004167	93.42	gold quality
primary visual cortex	UBERON:0002436	93.32	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.17	gold quality
blood	UBERON:0000178	93.11	gold quality
postcentral gyrus	UBERON:0002581	92.73	gold quality
parietal lobe	UBERON:0001872	92.60	gold quality
occipital lobe	UBERON:0002021	92.59	gold quality
frontal cortex	UBERON:0001870	92.23	gold quality
neocortex	UBERON:0001950	92.13	gold quality
cerebral cortex	UBERON:0000956	92.08	gold quality
temporal lobe	UBERON:0001871	91.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.53	gold quality
nucleus accumbens	UBERON:0001882	91.45	gold quality
telencephalon	UBERON:0001893	91.40	gold quality
right frontal lobe	UBERON:0002810	91.40	gold quality
synovial joint	UBERON:0002217	91.30	gold quality
cingulate cortex	UBERON:0003027	91.30	gold quality
anterior cingulate cortex	UBERON:0009835	91.10	gold quality
caudate nucleus	UBERON:0001873	90.72	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	77.81
E-HCAD-5	yes	53.17
E-CURD-46	yes	18.19
E-CURD-119	yes	4.73
E-CURD-88	yes	4.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

175 targeting CYRIA, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-539-5P	99.93	70.30	2855

Literature-anchored findings (GeneRIF, showing 2)

• confirmed that three genes (rs7922405 of MGMT, rs73039426 of RHPN2, and rs7552 of FAM49A) may contribute to nonsyndromic orofacial clefts in Chinese populations (PMID:29949196)
• CYRI-A limits invasive migration through macropinosome formation and integrin uptake regulation. (PMID:34165494)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam49a	ENSDARG00000006672
mus_musculus	Cyria	ENSMUSG00000020589
rattus_norvegicus	Cyria	ENSRNOG00000052758
drosophila_melanogaster	CG32066	FBGN0052066
caenorhabditis_elegans		WBGENE00019944

Paralogs (1): CYRIB (ENSG00000153310)

Protein

Protein identifiers

CYFIP-related Rac1 interactor A — Q9H0Q0 (reviewed: Q9H0Q0)

Alternative names: Protein CYRIA

All UniProt accessions (3): C9IYV6, C9JPE5, Q9H0Q0

UniProt curated annotations — full annotation on UniProt →

Function. May negatively regulate RAC1 signaling and RAC1-driven cytoskeletal remodeling. May regulate chemotaxis, cell migration and epithelial polarization by controlling the polarity, plasticity, duration and extent of protrusions.

Subunit / interactions. Interacts with RAC1 (GTP-bound form preferentially).

Subcellular location. Membrane.

Similarity. Belongs to the CYRI family.

RefSeq proteins (1): NP_110424* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009828	CYRIA/CYRIB_Rac1-bd	Domain
IPR039789	CYRI	Family

Pfam: PF07159

UniProt features (2 total): chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0Q0-F1	92.68	0.87

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 323 (showing top): AP1_01, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, MYOGENIN_Q6, CCAWYNNGAAR_UNKNOWN, AREB6_03, BROWNE_HCMV_INFECTION_16HR_UP, HNF1_Q6, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, AAAYRNCTG_UNKNOWN, FOXD3_01, ATGTTAA_MIR302C, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, DAVICIONI_RHABDOMYOSARCOMA_PAX_FOXO1_FUSION_UP

GO Biological Process (2): regulation of actin filament polymerization (GO:0030833), biological_process (GO:0008150)

GO Molecular Function (3): small GTPase binding (GO:0031267), molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (2): membrane (GO:0016020), cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of actin polymerization or depolymerization	1
actin filament polymerization	1
regulation of protein polymerization	1
GTPase binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

818 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYRIA	LRATD1	Q96KN4	560
CYRIA	RHPN2	Q8IUC4	540
CYRIA	MYCN	P04198	507
CYRIA	FAM227B	Q96M60	496
CYRIA	DDX1	Q92499	474
CYRIA	SPATS2L	Q9NUQ6	421
CYRIA	DCAF4L2	Q8NA75	419
CYRIA	PIK3C2G	O75747	411
CYRIA	CELA1	Q9UNI1	401
CYRIA	PPP1R1A	Q13522	389
CYRIA	VPS37D	Q86XT2	389
CYRIA	LRRIQ3	A6PVS8	380
CYRIA	RTTN	Q86VV8	380
CYRIA	CDO1	P78513	369
CYRIA	TSPAN12	O95859	358

IntAct

16 interactions, top by confidence:

A	B	Type	Score
CYRIA	CYRIB	psi-mi:“MI:0915”(physical association)	0.670
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
CYRIB	RAB3IL1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
CYRIB		psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
GPM6A	KIF2A	psi-mi:“MI:0914”(association)	0.350
CYRIB	PDC	psi-mi:“MI:0914”(association)	0.350
CD40	IPO5	psi-mi:“MI:0914”(association)	0.350
SCN2B	RIMOC1	psi-mi:“MI:0914”(association)	0.350
VSIG1	RIMOC1	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
LCOR	CYRIA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): FAM49A (Affinity Capture-MS), FAM49A (Affinity Capture-MS), FAM49A (Synthetic Lethality), FAM49A (Affinity Capture-MS), FAM49A (Affinity Capture-MS), FAM49A (Proximity Label-MS), FAM49A (Affinity Capture-MS), FAM49A (Biochemical Activity), FAM49A (Affinity Capture-MS), FAM49A (Two-hybrid), FAM49A (Affinity Capture-MS)

ESM2 similar proteins: A1ZAK1, B5X737, E1BGH8, E1C2Z0, E9Q3L2, O08662, O95379, P35608, P42173, P42356, Q13315, Q17QT7, Q2KJI3, Q3TBL6, Q4R7B1, Q4V847, Q5EB59, Q5MNV8, Q5R6L2, Q5RF18, Q5RIW8, Q5WNI9, Q5ZI04, Q5ZKU4, Q6DFE2, Q6P423, Q6PQD5, Q70CQ2, Q80V86, Q80YQ2, Q8BHZ0, Q8C4Y3, Q8GYM3, Q8N8J0, Q8QGX4, Q8T2H0, Q8WN22, Q921M7, Q921Z5, Q96N11

Diamond homologs: Q17QT7, Q2KJI3, Q5R6L2, Q5ZI04, Q8BHZ0, Q8T2H0, Q921M7, Q9H0Q0, Q9NUQ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	24
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1458517	NC_000002.11:g.(?15760332)(17692222_?)del	Pathogenic
686578	GRCh37/hg19 2p24.3-24.2(chr2:12269293-18259781)x3	Pathogenic
814222	GRCh37/hg19 2p24.3-24.2(chr2:15478363-17062394)x3	Pathogenic
812922	NC_000002.11:g.15744252_17675820del	Likely pathogenic

SpliceAI

2255 predictions. Top by Δscore:

Variant	Effect	Δscore
2:16559454:TCTTA:T	donor_loss	1.0000
2:16559455:CTTAC:C	donor_loss	1.0000
2:16559456:TTA:T	donor_loss	1.0000
2:16559457:TACAT:T	donor_loss	1.0000
2:16559458:A:AC	donor_gain	1.0000
2:16559458:A:AG	donor_loss	1.0000
2:16559459:C:CC	donor_gain	1.0000
2:16559459:CAT:C	donor_gain	1.0000
2:16559583:CTCC:C	acceptor_gain	1.0000
2:16560988:A:AC	donor_gain	1.0000
2:16560989:C:CC	donor_gain	1.0000
2:16561157:TTA:T	donor_loss	1.0000
2:16561158:TACTT:T	donor_loss	1.0000
2:16561159:A:AC	donor_gain	1.0000
2:16561160:C:CT	donor_gain	1.0000
2:16561160:CT:C	donor_gain	1.0000
2:16561160:CTT:C	donor_gain	1.0000
2:16561449:GACTC:G	donor_loss	1.0000
2:16561450:ACTCA:A	donor_loss	1.0000
2:16561451:CT:C	donor_loss	1.0000
2:16561452:TCA:T	donor_loss	1.0000
2:16561453:CA:C	donor_loss	1.0000
2:16561454:A:AC	donor_gain	1.0000
2:16561454:A:T	donor_loss	1.0000
2:16561455:C:CG	donor_gain	1.0000
2:16561455:CG:C	donor_gain	1.0000
2:16561455:CGT:C	donor_gain	1.0000
2:16561455:CGTG:C	donor_gain	1.0000
2:16561529:CTCAT:C	acceptor_gain	1.0000
2:16561530:TCAT:T	acceptor_gain	1.0000

AlphaMissense

2171 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:16559506:T:A	D264V	1.000
2:16559506:T:G	D264A	1.000
2:16561207:G:T	P195Q	1.000
2:16561489:T:A	R160S	1.000
2:16561489:T:G	R160S	1.000
2:16561490:C:A	R160I	1.000
2:16561490:C:G	R160T	1.000
2:16561492:T:A	R159S	1.000
2:16561492:T:G	R159S	1.000
2:16561493:C:A	R159I	1.000
2:16561493:C:G	R159T	1.000
2:16561501:G:C	S156R	1.000
2:16561501:G:T	S156R	1.000
2:16561503:T:G	S156R	1.000
2:16561510:A:C	N153K	1.000
2:16561510:A:T	N153K	1.000
2:16561513:C:A	Q152H	1.000
2:16561513:C:G	Q152H	1.000
2:16562005:C:A	K145N	1.000
2:16562005:C:G	K145N	1.000
2:16562015:T:A	D142V	1.000
2:16562016:C:G	D142H	1.000
2:16552996:G:C	F304L	0.999
2:16552996:G:T	F304L	0.999
2:16552998:A:G	F304L	0.999
2:16555072:A:G	L302P	0.999
2:16555072:A:T	L302H	0.999
2:16555117:A:G	L287S	0.999
2:16559481:G:C	F272L	0.999
2:16559481:G:T	F272L	0.999

dbSNP variants (sampled 300 via entrez): RS1000006315 (2:16600609 G>A,C), RS1000022390 (2:16662698 T>C), RS1000047528 (2:16622148 C>G), RS1000053382 (2:16662381 A>G), RS1000117408 (2:16620806 G>A), RS1000122504 (2:16558738 A>G), RS1000167149 (2:16550811 A>G), RS1000220843 (2:16590458 T>C), RS1000227793 (2:16630809 C>A,T), RS1000232977 (2:16604686 T>C), RS1000242777 (2:16604459 A>C), RS1000248113 (2:16557215 G>T), RS1000254765 (2:16656790 G>C), RS1000291576 (2:16650675 G>A), RS1000320827 (2:16650323 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): optic atrophy (MONDO:0003608)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002365_8	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 2 peripheral neuropathy)	8.000000e-06
GCST002842_10	Basal cell carcinoma	5.000000e-12
GCST004166_9	Nonsyndromic cleft lip with cleft palate	6.000000e-22
GCST005896_32	Non-melanoma skin cancer	5.000000e-08
GCST008059_254	Estimated glomerular filtration rate	3.000000e-10
GCST009379_13	Type 2 diabetes	1.000000e-08
GCST009462_27	Optic disc size	9.000000e-09
GCST011088_3	Orofacial clefts	3.000000e-08
GCST012337_2	Nonsyndromic cleft lip with or without cleft palate	4.000000e-10
GCST90013410_6	Basal cell carcinoma	2.000000e-25

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0003959	cleft lip
EFO:0009260	non-melanoma skin carcinoma

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	9
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	increases expression, affects expression	2
Estradiol	affects cotreatment, decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression, decreases expression	2
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects methylation	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
celastrol	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
ormosil	affects binding, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Aldehydes	increases expression	1
Calcitriol	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Formaldehyde	increases expression	1
Melphalan	decreases expression	1
Methapyrilene	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01834079	PHASE1/PHASE2	UNKNOWN	Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease
NCT04680143	PHASE1/PHASE2	COMPLETED	Systemic Erythropoietin Injection in Patients Having Optic Atrophy
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT04580979	Not specified	COMPLETED	Natural History Study of FDXR Mutation-related Mitochondriopathy
NCT04594590	Not specified	COMPLETED	Natural History Study of SLC25A46 Mutation-related Mitochondriopathy
NCT04723160	Not specified	COMPLETED	Computer Aided Diagnosis of Multiple Eye Fundus Diseases From Color Fundus Photograph
NCT06390579	Not specified	COMPLETED	Building Research With Artificial Intelligence in Neuro-Ophthalmology