ERICH3

Summary

ERICH3 (glutamate rich 3, HGNC:25346) is a protein-coding gene on chromosome 1p31.1, encoding Glutamate-rich protein 3 (Q5RHP9). Component of the primary cilium that controls cilium formation and length.

Involved in cilium assembly. Located in cytoplasm and non-motile cilium.

Source: NCBI Gene 127254 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 241 total
• MANE Select transcript: NM_001002912

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25346
Approved symbol	ERICH3
Name	glutamate rich 3
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547I048, RP11-653A5.1
Ensembl gene	ENSG00000178965
Ensembl biotype	protein_coding
OMIM	620866
Entrez	127254

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000326665, ENST00000420661, ENST00000433746, ENST00000479666, ENST00000614534

RefSeq mRNA: 1 — MANE Select: NM_001002912 NM_001002912

CCDS: CCDS30755

Canonical transcript exons

ENST00000326665 — 15 exons

Exon	Start	End
ENSE00001366041	74606601	74606902
ENSE00001367225	74612623	74612809
ENSE00001403696	74649222	74649315
ENSE00001405342	74643027	74643098
ENSE00001407414	74673497	74673792
ENSE00001408337	74636280	74636438
ENSE00001428105	74641331	74641459
ENSE00001429867	74646667	74646792
ENSE00001453838	74599695	74599931
ENSE00001730999	74576895	74576936
ENSE00001949164	74568123	74570439
ENSE00002246327	74589631	74590080
ENSE00003433707	74631713	74631928
ENSE00003590709	74620734	74620914
ENSE00003689734	74571099	74573491

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 99.32.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0359 / max 57.4145, expressed in 132 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12858	0.3473	92
12857	0.3436	93
12860	0.0948	59
12859	0.0779	55
12848	0.0495	26
12852	0.0418	26
12851	0.0276	16
12856	0.0257	4
12853	0.0171	5
12854	0.0066	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.32	gold quality
bronchus	UBERON:0002185	98.58	gold quality
middle temporal gyrus	UBERON:0002771	96.45	gold quality
right uterine tube	UBERON:0001302	95.88	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.82	gold quality
oviduct epithelium	UBERON:0004804	93.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.33	gold quality
left testis	UBERON:0004533	91.24	gold quality
right testis	UBERON:0004534	90.66	gold quality
superior frontal gyrus	UBERON:0002661	90.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.10	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.57	gold quality
postcentral gyrus	UBERON:0002581	88.86	gold quality
epithelium of nasopharynx	UBERON:0001951	88.71	gold quality
testis	UBERON:0000473	88.67	gold quality
entorhinal cortex	UBERON:0002728	87.70	gold quality
primary visual cortex	UBERON:0002436	87.56	gold quality
parietal lobe	UBERON:0001872	87.19	gold quality
nasal cavity epithelium	UBERON:0005384	86.53	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.93	gold quality
occipital lobe	UBERON:0002021	84.74	gold quality
prefrontal cortex	UBERON:0000451	84.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.97	gold quality
fallopian tube	UBERON:0003889	83.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.79	gold quality
nucleus accumbens	UBERON:0001882	83.79	gold quality
frontal cortex	UBERON:0001870	83.76	gold quality
cerebral cortex	UBERON:0000956	83.39	gold quality
neocortex	UBERON:0001950	83.30	gold quality
sperm	CL:0000019	83.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	62.21
E-GEOD-130148	yes	13.10
E-ANND-3	yes	11.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting ERICH3, 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-9-5P	100.00	72.28	2361
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-513A-5P	100.00	69.77	2465
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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-8082	99.95	67.27	1170

Literature-anchored findings (GeneRIF, showing 2)

• Enterovirus 71 VP1 promotes 5-HT release by upregulating the expression of ERICH3 and methyltransferase ZC3H13. (PMID:35660571)
• The ERICH3 rs11580409 polymorphism is associated with 6-month antidepressant response in depressed patients. (PMID:35878676)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	erich3	ENSDARG00000069262
mus_musculus	Erich3	ENSMUSG00000078161
rattus_norvegicus	Erich3	ENSRNOG00000009533

Protein

Protein identifiers

Glutamate-rich protein 3 — Q5RHP9 (reviewed: Q5RHP9)

All UniProt accessions (2): Q5RHP9, R4GMY5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the primary cilium that controls cilium formation and length. May function within retrograde intraflagellar transport (IFT)-associated pathways to remove signaling proteins from primary cilia. Also involved in neuronal vesicle biogenesis and neurotransmitter vesicular function.

Subunit / interactions. Interacts with CLTC/clathrin heavy chain 1, AP2A2/AP-2 complex subunit alpha-2, and PIK3C2A/phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha.

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Cilium axoneme.

Tissue specificity. Expressed in dopaminergic and serotoninergic neurons.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5RHP9-1	1	yes
Q5RHP9-2	2
Q5RHP9-3	3

RefSeq proteins (1): NP_001002912* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027962	ERICH3	Family
IPR048257	DUF4590	Domain

Pfam: PF15257

UniProt features (42 total): compositionally biased region 19, region of interest 9, sequence variant 6, splice variant 5, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5RHP9-F1	44.25	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_CYTOPLASMIC_REGION, GOCC_CILIUM, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOCC_NON_MOTILE_CILIUM, SNAPC4_TARGET_GENES, SRSF9_TARGET_GENES, GSE10240_CTRL_VS_IL22_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_UP, TERF1_TARGET_GENES

GO Biological Process (1): cilium assembly (GO:0060271)

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

GO Cellular Component (5): cytoplasm (GO:0005737), cilium (GO:0005929), axoneme (GO:0005930), non-motile cilium (GO:0097730), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
binding	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
cilium	1

Protein interactions and networks

STRING

1076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERICH3	TSPAN5	P62079	738
ERICH3	KLHL26	Q53HC5	543
ERICH3	CIMAP1D	Q3SX64	541
ERICH3	TAFA2	Q8N3H0	472
ERICH3	PLCD4	Q9BRC7	456
ERICH3	KLHL32	Q96NJ5	422
ERICH3	QPCT	Q16769	416
ERICH3	PLIN4	Q96Q06	412
ERICH3	SAXO2	Q658L1	409
ERICH3	CFAP210	Q0VFZ6	407
ERICH3	TEKT1	Q969V4	407
ERICH3	AGXT	P21549	396
ERICH3	CFAP77	Q6ZQR2	392
ERICH3	IQSEC3	Q9UPP2	385
ERICH3	CCDC17	Q96LX7	384

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ERICH3	HNRNPM	psi-mi:“MI:0915”(physical association)	0.400
ERICH3	HNRNPCL2	psi-mi:“MI:0915”(physical association)	0.400
Tuba3a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Bach1	SYNM	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ERICH3	MDM2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): ERICH3 (Affinity Capture-MS), ERICH3 (Affinity Capture-MS), ERICH3 (Affinity Capture-MS), ERICH3 (Proximity Label-MS), ERICH3 (Proximity Label-MS), ERICH3 (Proximity Label-MS), ERICH3 (Cross-Linking-MS (XL-MS)), ERICH3 (Cross-Linking-MS (XL-MS)), ERICH3 (Affinity Capture-MS)

ESM2 similar proteins: A0JM80, A6H8Y1, A7MBJ2, D3ZF42, E9Q6J5, F4I700, F4J3S1, F4KCE9, F6QRE9, O04251, O82345, P23497, P46100, P48785, P48786, Q04996, Q05B65, Q0WTB8, Q13342, Q15361, Q32MZ4, Q3UZ39, Q3ZBR9, Q4QSC8, Q571C7, Q5H9K5, Q5RHP9, Q61687, Q66HF9, Q7YQM3, Q7YQM4, Q7Z5L2, Q8BJM3, Q8C4A5, Q8C9B9, Q8GZ87, Q8H991, Q8IW19, Q92576, Q940Y3

Diamond homologs: F6QRE9, Q5RHP9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	215
Likely benign	17
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2688 predictions. Top by Δscore:

Variant	Effect	Δscore
1:74589701:A:AC	donor_gain	1.0000
1:74589702:C:CC	donor_gain	1.0000
1:74589702:CT:C	donor_gain	1.0000
1:74589707:AT:A	donor_gain	1.0000
1:74599709:T:TA	donor_gain	1.0000
1:74599928:TACT:T	acceptor_gain	1.0000
1:74599930:CT:C	acceptor_gain	1.0000
1:74599932:C:CC	acceptor_gain	1.0000
1:74620912:ATCC:A	acceptor_loss	1.0000
1:74620913:TC:T	acceptor_gain	1.0000
1:74620913:TCC:T	acceptor_loss	1.0000
1:74620914:CC:C	acceptor_gain	1.0000
1:74620915:C:A	acceptor_loss	1.0000
1:74641325:ACT:A	donor_loss	1.0000
1:74641327:TCA:T	donor_loss	1.0000
1:74641328:CA:C	donor_loss	1.0000
1:74641329:A:AC	donor_gain	1.0000
1:74641329:ACC:A	donor_loss	1.0000
1:74641330:C:A	donor_loss	1.0000
1:74641330:C:CC	donor_gain	1.0000
1:74641330:CCA:C	donor_gain	1.0000
1:74641457:TCCC:T	acceptor_loss	1.0000
1:74641459:CCTA:C	acceptor_loss	1.0000
1:74641461:T:A	acceptor_loss	1.0000
1:74643021:CCTTA:C	donor_loss	1.0000
1:74643022:CTTA:C	donor_loss	1.0000
1:74643023:TTACC:T	donor_loss	1.0000
1:74643024:TACC:T	donor_loss	1.0000
1:74643025:A:T	donor_loss	1.0000
1:74643026:C:CA	donor_loss	1.0000

AlphaMissense

10051 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:74606901:A:G	C397R	0.999
1:74612628:G:C	C394W	0.999
1:74612630:A:G	C394R	0.999
1:74612712:A:C	C366W	0.999
1:74612713:C:T	C366Y	0.999
1:74612714:A:G	C366R	0.999
1:74612717:A:G	C365R	0.999
1:74612761:A:G	L350P	0.999
1:74612763:A:C	S349R	0.999
1:74612763:A:T	S349R	0.999
1:74612765:T:G	S349R	0.999
1:74612797:A:G	F338S	0.999
1:74612803:A:G	F336S	0.999
1:74606899:G:C	C397W	0.998
1:74606900:C:G	C397S	0.998
1:74606901:A:T	C397S	0.998
1:74612629:C:T	C394Y	0.998
1:74612661:A:C	F383L	0.998
1:74612661:A:T	F383L	0.998
1:74612662:A:G	F383S	0.998
1:74612663:A:G	F383L	0.998
1:74612713:C:A	C366F	0.998
1:74612713:C:G	C366S	0.998
1:74612714:A:T	C366S	0.998
1:74612715:A:C	C365W	0.998
1:74612716:C:T	C365Y	0.998
1:74612721:G:C	S363R	0.998
1:74612721:G:T	S363R	0.998
1:74612723:T:G	S363R	0.998
1:74612772:G:C	F346L	0.998

dbSNP variants (sampled 300 via entrez): RS1000035053 (1:74673823 G>A), RS1000234692 (1:74651912 C>A,T), RS1000244483 (1:74651538 C>T), RS1000339832 (1:74652234 T>C), RS1000381648 (1:74663093 T>C), RS1000387142 (1:74652596 T>C), RS1000397762 (1:74646280 C>A,T), RS1000411208 (1:74574317 T>A,C), RS1000433128 (1:74663629 A>G), RS1000461631 (1:74614021 A>G), RS1000462744 (1:74659275 C>A), RS1000469873 (1:74591180 C>T), RS1000472537 (1:74667797 G>C), RS1000488170 (1:74574104 C>T), RS1000519384 (1:74618662 G>A,C)

Disease associations

OMIM: gene MIM:620866 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004862_35	Itch intensity from mosquito bite adjusted by bite size	5.000000e-07
GCST005950_6	Body mass index x sex x age interaction (4df test)	1.000000e-15
GCST005951_197	Body mass index	4.000000e-13
GCST005953_11	Body mass index (age <50)	3.000000e-15
GCST005954_3	Body mass index x age interaction	3.000000e-06
GCST007327_185	Smoking status (ever vs never smokers)	6.000000e-12
GCST010396_66	Gut microbiota (bacterial taxa, hurdle binary method)	8.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004318	smoking behavior
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11580409	Efficacy	3	antidepressants	Depressive Disorder
rs696692	Efficacy	3	citalopram;escitalopram	Depressive Disorder

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs696692	ERICH3	3	0.00	1	citalopram;escitalopram
rs11580409	ERICH3	3	6.00	1	antidepressants

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, increases methylation, decreases expression	3
Valproic Acid	affects expression, decreases methylation	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
decabromobiphenyl ether	decreases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Carbamazepine	affects expression	1
Demecolcine	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Vincristine	decreases expression	1
Zearalenone	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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