CHIC1

Summary

CHIC1 (cysteine rich hydrophobic domain 1, HGNC:1934) is a protein-coding gene on chromosome Xq13.2, encoding Cysteine-rich hydrophobic domain-containing protein 1 (Q5VXU3).

This gene encodes a cysteine-rich hydrophobic (CHIC) domain-containing protein, and is one of the few protein-coding genes found near the X-inactivation center. Studies in mouse indicate that the mouse ortholog of this gene is subject to X-inactivation in mouse. Experiments with other CHIC domain-containing family members show that the cysteine residues are palmitoylated post-translationally, resulting in membrane association. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 53344 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_001039840

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1934
Approved symbol	CHIC1
Name	cysteine rich hydrophobic domain 1
Location	Xq13.2
Locus type	gene with protein product
Status	Approved
Aliases	BRX
Ensembl gene	ENSG00000204116
Ensembl biotype	protein_coding
OMIM	300922
Entrez	53344

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 nonsense_mediated_decay

ENST00000373502, ENST00000373504, ENST00000498318, ENST00000498407

RefSeq mRNA: 2 — MANE Select: NM_001039840 NM_001039840, NM_001300884

CCDS: CCDS35335, CCDS75993

Canonical transcript exons

ENST00000373502 — 6 exons

Exon	Start	End
ENSE00001460708	73563197	73563580
ENSE00001727774	73680955	73687111
ENSE00003314922	73577407	73577461
ENSE00003504272	73584417	73584572
ENSE00003587744	73679654	73679713
ENSE00003590023	73679326	73679382

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 98.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5007 / max 287.0723, expressed in 1564 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196733	5.6381	1367
196732	1.6828	850
196730	0.4289	200
196731	0.3887	187
196734	0.2252	107
196735	0.1370	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.30	gold quality
oviduct epithelium	UBERON:0004804	95.35	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.16	gold quality
epithelial cell of pancreas	CL:0000083	93.76	gold quality
middle temporal gyrus	UBERON:0002771	92.17	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.77	gold quality
oocyte	CL:0000023	89.28	gold quality
primary visual cortex	UBERON:0002436	89.08	gold quality
germinal epithelium of ovary	UBERON:0001304	88.83	gold quality
secondary oocyte	CL:0000655	88.69	gold quality
occipital lobe	UBERON:0002021	88.15	gold quality
pons	UBERON:0000988	86.95	gold quality
substantia nigra pars compacta	UBERON:0001965	86.14	gold quality
medial globus pallidus	UBERON:0002477	85.96	gold quality
calcaneal tendon	UBERON:0003701	85.31	gold quality
globus pallidus	UBERON:0001875	85.18	gold quality
prefrontal cortex	UBERON:0000451	84.94	gold quality
superior frontal gyrus	UBERON:0002661	84.70	gold quality
tibia	UBERON:0000979	84.52	gold quality
tendon	UBERON:0000043	84.48	gold quality
lateral globus pallidus	UBERON:0002476	84.39	gold quality
substantia nigra pars reticulata	UBERON:0001966	84.24	gold quality
parietal pleura	UBERON:0002400	84.18	gold quality
cerebellar vermis	UBERON:0004720	83.45	gold quality
parietal lobe	UBERON:0001872	83.43	gold quality
postcentral gyrus	UBERON:0002581	83.38	gold quality
entorhinal cortex	UBERON:0002728	83.03	gold quality
superior vestibular nucleus	UBERON:0007227	83.00	gold quality
cauda epididymis	UBERON:0004360	82.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

458 targeting CHIC1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
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-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	chic1	ENSDARG00000053166
mus_musculus	Chic1	ENSMUSG00000031327
rattus_norvegicus	Chic1	ENSRNOG00000037919
drosophila_melanogaster	CG5938	FBGN0046247
caenorhabditis_elegans		WBGENE00044319

Paralogs (1): CHIC2 (ENSG00000109220)

Protein

Protein identifiers

Cysteine-rich hydrophobic domain-containing protein 1 — Q5VXU3 (reviewed: Q5VXU3)

Alternative names: Brain X-linked protein

All UniProt accessions (3): B7Z4S5, Q5VXU3, R4GN46

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane. Cytoplasmic vesicle.

Tissue specificity. Equally expressed in various parts of the brain.

Post-translational modifications. Palmitoylated.

Similarity. Belongs to the CHIC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VXU3-1	1	yes
Q5VXU3-2	2

RefSeq proteins (2): NP_001034929, NP_001287813 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019383	Golgin_A_7/ERF4	Domain
IPR039735	CHIC1/2	Family

Pfam: PF10256

UniProt features (7 total): compositionally biased region 3, chain 1, region of interest 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VXU3-F1	74.69	0.34

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 229 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GCM_RING1, GCM_TEC, GCM_CDH5, KAYO_AGING_MUSCLE_UP, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, YOSHIMURA_MAPK8_TARGETS_UP, GCM_BNIP1, GCM_FANCC, chrXq13, BAKKER_FOXO3_TARGETS_UP, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, GCM_HMGA2, GSE13522_CTRL_VS_T_CRUZI_BRAZIL_STRAIN_INF_SKIN_DN, GSE13522_WT_VS_IFNAR_KO_SKIN_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHIC1	RLIM	Q9NVW2	690
CHIC1	CDX4	O14627	576
CHIC1	SLC16A2	P36021	555
CHIC1	ZCCHC13	Q8WW36	519
CHIC1	DLG3	Q92796	458
CHIC1	SLC7A3	Q8WY07	433
CHIC1	CHID1	Q9BWS9	427
CHIC1	WASF3	Q9UPY6	412
CHIC1	NEXMIF	Q5QGS0	406
CHIC1	DMRTC1	Q5HYR2	396
CHIC1	ABCB7	O75027	373
CHIC1	TAF9B	Q9HBM6	372
CHIC1	PDZRN3	Q9UPQ7	352
CHIC1	YIPF6	Q96EC8	351
CHIC1	CEP15	Q9HBI5	339

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CHIC1	TXNDC9	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): KIAA0232 (Affinity Capture-MS), ZNF92 (Affinity Capture-MS), TXNDC9 (Affinity Capture-MS), USP1 (Affinity Capture-MS), STIP1 (Affinity Capture-MS), NUFIP1 (Affinity Capture-MS), BBX (Affinity Capture-MS), MCM9 (Affinity Capture-MS), KIAA1279 (Affinity Capture-MS), POLR3A (Affinity Capture-MS), DMWD (Affinity Capture-MS), URI1 (Affinity Capture-MS), CHIC1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A8I6A2H6, A2A7Q9, A7E2I7, F1M8G0, O08873, O14795, P17863, P49140, P49805, P54368, P55814, Q05DH4, Q08B84, Q2M146, Q3C2P8, Q49LS4, Q4KUS2, Q505K2, Q5GH67, Q5GH76, Q5RDN2, Q5RH73, Q5TF58, Q5VXU3, Q5ZKN3, Q62739, Q62768, Q62769, Q66JG9, Q68FE7, Q6NRE7, Q6NYK3, Q7Z698, Q86XE3, Q8CB19, Q8CBW7, Q8CDD8, Q8IW70, Q8R2V2, Q8WXG6

Diamond homologs: Q5VXU3, Q8CBW7, Q9D9G3, Q9UKJ5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1405 predictions. Top by Δscore:

Variant	Effect	Δscore
X:73563441:G:GT	donor_gain	1.0000
X:73563474:G:GT	donor_gain	1.0000
X:73563480:G:GT	donor_gain	1.0000
X:73563483:G:GT	donor_gain	1.0000
X:73563486:G:GT	donor_gain	1.0000
X:73582355:ATTT:A	acceptor_gain	1.0000
X:73584411:TTGTA:T	acceptor_loss	1.0000
X:73584412:TGTA:T	acceptor_loss	1.0000
X:73584413:GTAG:G	acceptor_loss	1.0000
X:73584414:TAGGT:T	acceptor_loss	1.0000
X:73584415:A:C	acceptor_loss	1.0000
X:73584416:G:GA	acceptor_loss	1.0000
X:73584571:GA:G	donor_gain	1.0000
X:73584573:G:GG	donor_gain	1.0000
X:73563432:G:GT	donor_gain	0.9900
X:73563456:G:GT	donor_gain	0.9900
X:73563465:G:GT	donor_gain	0.9900
X:73563468:G:GT	donor_gain	0.9900
X:73563471:G:GT	donor_gain	0.9900
X:73563579:GT:G	donor_gain	0.9900
X:73563581:G:GG	donor_gain	0.9900
X:73577459:AAGGT:A	donor_loss	0.9900
X:73577460:AGGTA:A	donor_loss	0.9900
X:73577461:GGT:G	donor_loss	0.9900
X:73577462:G:T	donor_loss	0.9900
X:73577463:TAAG:T	donor_loss	0.9900
X:73582348:A:AG	acceptor_gain	0.9900
X:73582358:T:A	acceptor_gain	0.9900
X:73584415:A:AG	acceptor_gain	0.9900
X:73584415:AGGT:A	acceptor_gain	0.9900

AlphaMissense

1463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:73577427:T:C	F106S	1.000
X:73577451:T:C	L114P	1.000
X:73584508:G:A	G148D	1.000
X:73584540:A:C	S159R	1.000
X:73584542:C:A	S159R	1.000
X:73584542:C:G	S159R	1.000
X:73679666:T:A	W193R	1.000
X:73679666:T:C	W193R	1.000
X:73577412:G:A	G101D	0.999
X:73577415:T:C	L102S	0.999
X:73577426:T:C	F106L	0.999
X:73577427:T:G	F106C	0.999
X:73577428:T:A	F106L	0.999
X:73577428:T:G	F106L	0.999
X:73577438:T:C	F110L	0.999
X:73577439:T:C	F110S	0.999
X:73577440:T:A	F110L	0.999
X:73577440:T:G	F110L	0.999
X:73577451:T:A	L114Q	0.999
X:73577451:T:G	L114R	0.999
X:73577457:G:A	G116E	0.999
X:73584421:C:A	A119D	0.999
X:73584433:T:C	F123S	0.999
X:73584441:A:C	S126R	0.999
X:73584443:C:A	S126R	0.999
X:73584443:C:G	S126R	0.999
X:73584495:T:A	W144R	0.999
X:73584495:T:C	W144R	0.999
X:73584499:T:C	L145P	0.999
X:73584507:G:C	G148R	0.999

dbSNP variants (sampled 300 via entrez): RS1000030205 (X:73593787 T>G), RS1000032735 (X:73620975 A>G,T), RS1000061785 (X:73686731 G>A), RS1000092527 (X:73581846 TG>T), RS1000097949 (X:73619156 T>C), RS1000123201 (X:73628840 A>G), RS1000163821 (X:73660443 A>G), RS1000212128 (X:73667790 C>A,G), RS1000222863 (X:73568782 A>G), RS1000257536 (X:73660688 C>G), RS1000274284 (X:73648527 C>A), RS1000309103 (X:73564876 A>C), RS1000366311 (X:73637698 G>C,T), RS1000371262 (X:73612214 G>C), RS1000375355 (X:73659795 T>A)

Disease associations

OMIM: gene MIM:300922 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	4
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
Sunitinib	decreases expression	1
Glyphosate	decreases expression	1
Cadmium	increases abundance, increases expression	1
Clorgyline	increases expression	1
Copper	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Formaldehyde	decreases expression	1
Methapyrilene	decreases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer