CXorf65

Summary

CXorf65 (chromosome X open reading frame 65, HGNC:33713) is a protein-coding gene on chromosome Xq13.1, encoding Uncharacterized protein CXorf65 (A6NEN9).

Predicted to enable RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to act upstream of or within transcription by RNA polymerase II.

Source: NCBI Gene 158830 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 20 total — 2 pathogenic
• MANE Select transcript: NM_001025265

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33713
Approved symbol	CXorf65
Name	chromosome X open reading frame 65
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204165
Ensembl biotype	protein_coding
OMIM	301160
Entrez	158830

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 retained_intron, 1 protein_coding, 1 nonsense_mediated_decay

ENST00000374251, ENST00000438526, ENST00000466160, ENST00000483257

RefSeq mRNA: 1 — MANE Select: NM_001025265 NM_001025265

CCDS: CCDS35324

Canonical transcript exons

ENST00000374251 — 6 exons

Exon	Start	End
ENSE00001462915	71104298	71104404
ENSE00001462922	71106340	71106426
ENSE00001462923	71106532	71106740
ENSE00003499506	71103889	71104112
ENSE00003704521	71106000	71106137
ENSE00003709448	71104769	71104837

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 93.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0836 / max 85.7061, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199542	0.0755	4
199541	0.0081	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.36	gold quality
left testis	UBERON:0004533	89.24	gold quality
testis	UBERON:0000473	88.85	gold quality
right testis	UBERON:0004534	88.59	gold quality
blood	UBERON:0000178	83.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.26	gold quality
bone marrow	UBERON:0002371	79.68	gold quality
spleen	UBERON:0002106	79.28	gold quality
bone marrow cell	CL:0002092	75.58	gold quality
right lung	UBERON:0002167	71.45	gold quality
vermiform appendix	UBERON:0001154	70.11	gold quality
lymph node	UBERON:0000029	69.14	gold quality
small intestine Peyer’s patch	UBERON:0003454	68.81	gold quality
leukocyte	CL:0000738	67.37	gold quality
rectum	UBERON:0001052	67.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	67.08	gold quality
small intestine	UBERON:0002108	66.74	gold quality
monocyte	CL:0000576	65.86	gold quality
upper lobe of left lung	UBERON:0008952	64.94	gold quality
subcutaneous adipose tissue	UBERON:0002190	61.77	gold quality
left uterine tube	UBERON:0001303	61.35	gold quality
right coronary artery	UBERON:0001625	59.66	gold quality
lung	UBERON:0002048	59.53	gold quality
adipose tissue	UBERON:0001013	58.43	gold quality
gall bladder	UBERON:0002110	58.39	gold quality
placenta	UBERON:0001987	58.16	gold quality
lower esophagus mucosa	UBERON:0035834	57.94	gold quality
duodenum	UBERON:0002114	57.15	gold quality
skin of leg	UBERON:0001511	56.90	gold quality
zone of skin	UBERON:0000014	56.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.62

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	C14HXorf65	ENSDARG00000090981
mus_musculus	Gm614	ENSMUSG00000090141
rattus_norvegicus	Cxhxorf65	ENSRNOG00000084557

Protein

Protein identifiers

Uncharacterized protein CXorf65 — A6NEN9 (reviewed: A6NEN9)

All UniProt accessions (2): A6NEN9, C9J8K0

RefSeq proteins (1): NP_001020436* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR039471	CXorf65-like	Family

Pfam: PF15874

UniProt features (4 total): chain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NEN9-F1	82.63	0.67

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MARTENS_TRETINOIN_RESPONSE_DN, chrXq13, ATF6_TARGET_GENES, GSE16755_CTRL_VS_IFNA_TREATED_MAC_DN, DESCARTES_FETAL_PANCREAS_LYMPHOID_CELLS, THAKAR_PBMC_INACTIVATED_INFLUENZA_AGE_21_30YO_RESPONDERS_28DY_DN, THAKAR_PBMC_INACTIVATED_INFLUENZA_AGE_21_30YO_RESPONDERS_7DY_DN, NAKAYA_PBMC_FLUARIX_FLUVIRIN_AGE_18_50YO_CORRELATED_WITH_HAI_28DY_RESPONSE_AT_7DY_NEGATIVE, NAKAYA_PBMC_FLUARIX_FLUVIRIN_AGE_18_50YO_3DY_DN, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GSE29617_CTRL_VS_DAY3_TIV_FLU_VACCINE_PBMC_2008_UP, GSE29617_DAY3_VS_DAY7_TIV_FLU_VACCINE_PBMC_2008_DN, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GSE37416_CTRL_VS_6H_F_TULARENSIS_LVS_NEUTROPHIL_DN

GO Biological Process (2): transcription by RNA polymerase II (GO:0006366), gene expression (GO:0010467)

GO Molecular Function (1): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
macromolecule biosynthetic process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1

Protein interactions and networks

STRING

202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXorf65	CCDC187	A0A096LP49	544
CXorf65	C20orf173	Q96LM9	544
CXorf65	TMCO2	Q7Z6W1	541
CXorf65	ZC3H11D	Q8NA57	518
CXorf65	FAM209A	Q5JX71	517
CXorf65	SMCO2	A6NFE2	513
CXorf65	CCDC54	Q8NEL0	507
CXorf65	CIMIP4	O43247	507
CXorf65	SPATA31G1	Q5VYM1	479
CXorf65	C22orf23	Q9BZE7	479
CXorf65	ARRDC5	A6NEK1	474
CXorf65	FAM81B	Q96LP2	473
CXorf65	CCDC90B	Q9GZT6	473
CXorf65	GARIN1B	Q96KD3	446
CXorf65	SHCBP1L	Q9BZQ2	445

IntAct

0 interactions, top by confidence:

BioGRID (5): TLK1 (Cross-Linking-MS (XL-MS)), EVL (Cross-Linking-MS (XL-MS)), RPS6 (Cross-Linking-MS (XL-MS)), IQCF5 (Cross-Linking-MS (XL-MS)), CXorf65 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1B7XV12, A0A571BF63, A0A5F8MPE6, A0JMA8, A3KQ58, A6NEN9, A6QNM3, A8E7C5, A8PJX4, B0W730, O00443, O00522, O59800, P70371, Q08AE8, Q0VA04, Q0VA42, Q14D04, Q16YA8, Q32LJ3, Q3V2K1, Q4R707, Q52KF3, Q5F3E8, Q5PQS3, Q5RAY1, Q5UQM6, Q5XIR8, Q61QK6, Q63ZP1, Q6C4Q6, Q6DTM3, Q6ING4, Q6NSI8, Q6S5J6, Q6TNJ1, Q6ZUI0, Q7Z3E5, Q7ZXG4, Q86VD1

Diamond homologs: A6NEN9, Q32LJ3, Q3V2K1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	4
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
265194	NM_000206.3(IL2RG):c.270-15A>G	Pathogenic
3244127	NC_000023.10:g.(?70326254)(70332481_?)del	Pathogenic

SpliceAI

942 predictions. Top by Δscore:

Variant	Effect	Δscore
X:71104113:C:CC	acceptor_gain	1.0000
X:71104402:CAA:C	acceptor_gain	1.0000
X:71104405:C:CC	acceptor_gain	1.0000
X:71106023:CAAA:C	donor_gain	1.0000
X:71104108:TTGGA:T	acceptor_gain	0.9900
X:71104109:TGGA:T	acceptor_gain	0.9900
X:71104110:GGA:G	acceptor_gain	0.9900
X:71104110:GGAC:G	acceptor_loss	0.9900
X:71104111:GA:G	acceptor_gain	0.9900
X:71104112:ACT:A	acceptor_gain	0.9900
X:71104112:ACTAG:A	acceptor_loss	0.9900
X:71104400:TGCAA:T	acceptor_gain	0.9900
X:71106022:A:AC	donor_gain	0.9900
X:71106023:C:CC	donor_gain	0.9900
X:71106338:A:AC	donor_gain	0.9900
X:71106339:C:CC	donor_gain	0.9900
X:71106357:A:AC	donor_gain	0.9900
X:71106358:C:CC	donor_gain	0.9900
X:71106358:CTTTA:C	donor_gain	0.9900
X:71106362:A:AC	donor_gain	0.9900
X:71106363:C:CC	donor_gain	0.9900
X:71106533:T:TA	donor_gain	0.9900
X:71104111:GACT:G	acceptor_gain	0.9800
X:71104113:C:A	acceptor_gain	0.9800
X:71104291:GTCTT:G	donor_loss	0.9800
X:71104292:TCTTA:T	donor_loss	0.9800
X:71104293:CTTAC:C	donor_loss	0.9800
X:71104294:TTAC:T	donor_loss	0.9800
X:71104295:TAC:T	donor_loss	0.9800
X:71104296:A:AT	donor_loss	0.9800

AlphaMissense

1201 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:71106551:G:C	F2L	0.995
X:71106551:G:T	F2L	0.995
X:71106553:A:G	F2L	0.995
X:71106125:A:G	L42S	0.989
X:71106091:G:C	F53L	0.988
X:71106091:G:T	F53L	0.988
X:71106093:A:G	F53L	0.988
X:71106024:A:G	C76R	0.987
X:71106414:A:G	F13S	0.987
X:71106404:A:C	N16K	0.986
X:71106404:A:T	N16K	0.986
X:71106408:A:T	V15D	0.985
X:71106062:G:T	A63D	0.982
X:71106543:A:T	I5N	0.981
X:71104801:G:C	P96R	0.980
X:71106413:A:C	F13L	0.980
X:71106413:A:T	F13L	0.980
X:71106415:A:G	F13L	0.980
X:71106552:A:G	F2S	0.980
X:71106026:A:T	V75D	0.979
X:71106110:C:A	G47V	0.978
X:71106050:A:G	L67P	0.977
X:71106111:C:A	G47W	0.977
X:71106022:A:C	C76W	0.976
X:71104801:G:T	P96H	0.974
X:71106395:A:C	C19W	0.973
X:71106552:A:C	F2C	0.972
X:71106123:A:G	C43R	0.971
X:71106128:T:A	D41V	0.970
X:71106128:T:C	D41G	0.970

dbSNP variants (sampled 300 via entrez): RS1002172384 (X:71107905 G>A), RS1002550206 (X:71105883 T>A,G), RS1002578584 (X:71103708 A>C), RS1003538083 (X:71106349 G>A), RS1003574476 (X:71105250 AAAAT>A,AAAATAAAT), RS1003634068 (X:71105913 G>C), RS1004896505 (X:71105611 C>T), RS1006384082 (X:71103823 C>A,G), RS1007533014 (X:71107204 C>A,T), RS1007814650 (X:71105181 G>T), RS1007819130 (X:71103828 A>C,T), RS1008792649 (X:71106893 T>C), RS1010143678 (X:71103676 G>A), RS1011311652 (X:71105143 G>C), RS1016414441 (X:71103832 G>C)

Disease associations

OMIM: gene MIM:301160 | disease phenotypes: MIM:305450, MIM:300400

GenCC curated gene-disease

Mondo (2): FG syndrome 1 (MONDO:0010590), T-B+ severe combined immunodeficiency due to gamma chain deficiency (MONDO:0010315)

Orphanet (2): FG syndrome type 1 (Orphanet:93932), T-B+ severe combined immunodeficiency due to gamma chain deficiency (Orphanet:276)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
Air Pollutants, Occupational	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Silicon Dioxide	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00008450	PHASE1	COMPLETED	Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
NCT03601286	PHASE1	RECRUITING	Lentiviral Gene Therapy for X-linked Severe Combined Immunodeficiency
NCT00490100	PHASE1/PHASE2	TERMINATED	Treatment for Growth Failure in Patients With X-Linked Severe Combined Immunodeficiency: Phase 2 Study of Insulin-Like Growth Factor-1
NCT01306019	PHASE1/PHASE2	RECRUITING	Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)
NCT01410019	PHASE1/PHASE2	COMPLETED	Gene Therapy for X-linked Severe Combined Immunodeficiency
NCT03311503	PHASE1/PHASE2	RECRUITING	Phase I/II Trial of Lentiviral Gene Transfer for SCID-X1 With Low Dose Targeted Busulfan Conditioning
NCT06851767	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Base-Edited Hematopoietic Stem/Progenitor Cell X-Linked Severe Combined Immunodeficiency Gene Therapy
NCT01175239	Not specified	UNKNOWN	Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1)
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns