RBMXL2

Summary

RBMXL2 (RBMX like 2, HGNC:17886) is a protein-coding gene on chromosome 11p15.4, encoding RNA-binding motif protein, X-linked-like-2 (O75526). RNA-binding protein involved in alternative splicing in the testis during spermatogenesis.

This gene belongs to the HNRPG subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two RRM domains that bind RNAs. This gene is intronless and is thought to be derived from a processed retroposon. However, unlike many retroposon-derived genes, this gene is not a pseudogene. The encoded protein has similarity to HNRPG and RBMY proteins and it is suggested to replace HNRPG protein function during meiotic prophase or act as a germ cell-specific splicing regulator. It primarily localizes to the nuclei of meiotic spermatocytes. This gene is a candidate for autosomal male infertility.

Source: NCBI Gene 27288 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• MANE Select transcript: NM_014469

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17886
Approved symbol	RBMXL2
Name	RBMX like 2
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	HNRNPG-T, HNRPGT
Ensembl gene	ENSG00000170748
Ensembl biotype	protein_coding
OMIM	605444
Entrez	27288

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000306904

RefSeq mRNA: 1 — MANE Select: NM_014469 NM_014469

CCDS: CCDS7777

Canonical transcript exons

ENST00000306904 — 1 exons

Exon	Start	End
ENSE00001423034	7088998	7091148

Expression profiles

Bgee: expression breadth broad, 22 present calls, max score 95.72.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2126 / max 207.9502, expressed in 7 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112884	0.1436	6
112886	0.0592	5
112885	0.0080	4
112883	0.0018	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.72	gold quality
male germ cell	CL:0000015	93.42	gold quality
adult organism	UBERON:0007023	90.18	gold quality
right testis	UBERON:0004534	88.21	gold quality
left testis	UBERON:0004533	88.02	gold quality
testis	UBERON:0000473	86.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.89	silver quality
gingival epithelium	UBERON:0001949	55.82	gold quality
germinal epithelium of ovary	UBERON:0001304	55.25	gold quality
bone marrow cell	CL:0002092	51.57	gold quality
gingiva	UBERON:0001828	51.28	gold quality
pancreatic ductal cell	CL:0002079	50.88	silver quality
epithelial cell of pancreas	CL:0000083	49.62	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
quadriceps femoris	UBERON:0001377	49.28	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
thymus	UBERON:0002370	48.90	gold quality
vastus lateralis	UBERON:0001379	48.88	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	27.49
E-ANND-3	yes	2.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting RBMXL2, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-6513-5P	99.43	67.81	1071

Literature-anchored findings (GeneRIF, showing 4)

• Heterogeneous nuclear ribonucleoprotein G-T (hnRNP G-T) is a germ cell-specific protein expressed most prominently during meiosis (PMID:12389739)
• germ cell-specific RBMY and hnRNP G-T proteins were more efficient in stimulating TLE4-T incorporation than somatically expressed hnRNP G protein. (PMID:19893608)
• nuclear hnRNP G level as well as hTra2-beta1 level were independent prognostic factors for endometrial cancer progression-free survival (PMID:20607830)
• The initial recruitment of hnRNP G to nascent pre-mRNAs is independent of its sequence-specific RNA binding properties. (PMID:21327109)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rbmxl2	ENSMUSG00000073894
rattus_norvegicus	Rbmxl2	ENSRNOG00000090098

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), HNRNPA2B1 (ENSG00000122566), RBM19 (ENSG00000122965), RBM39 (ENSG00000131051), MSI1 (ENSG00000135097), HNRNPA1 (ENSG00000135486), HNRNPD (ENSG00000138668), HNRNPA1L2 (ENSG00000139675), RBMX (ENSG00000147274), A1CF (ENSG00000148584), TIAL1 (ENSG00000151923), RBM46 (ENSG00000151962), HNRNPDL (ENSG00000152795), MSI2 (ENSG00000153944), RBM47 (ENSG00000163694), RBMY1F (ENSG00000169800), HNRNPA3 (ENSG00000170144), RBM4B (ENSG00000173914), RBM4 (ENSG00000173933), RBMXL3 (ENSG00000175718), HNRNPA0 (ENSG00000177733), TRNAU1AP (ENSG00000180098), HNRNPAB (ENSG00000197451), RBMXL1 (ENSG00000213516), HNRNPA1L3 (ENSG00000224578), RBMY1J (ENSG00000226941), RBMY1A1 (ENSG00000234414), RBMY1E (ENSG00000242389), RBMY1B (ENSG00000242875), RBMY1D (ENSG00000244395), DND1 (ENSG00000256453)

Protein

Protein identifiers

RNA-binding motif protein, X-linked-like-2 — O75526 (reviewed: O75526)

Alternative names: Testis-specific heterogeneous nuclear ribonucleoprotein G-T

All UniProt accessions (1): O75526

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein involved in alternative splicing in the testis during spermatogenesis.

Subcellular location. Nucleus.

Tissue specificity. Expressed predominantly in spermatocytes and less in round spermatids (at protein level). Expressed in germ cells.

RefSeq proteins (1): NP_055284* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR003954	RRM_euk-type	Domain
IPR012604	RBM1CTR	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050441	RBM	Family

Pfam: PF00076, PF08081

UniProt features (13 total): compositionally biased region 6, sequence variant 4, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75526-F1	54.45	0.08

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 86 (showing top): RRAGTTGT_UNKNOWN, FOXO4_01, MODULE_379, GOBP_RNA_SPLICING, GNF2_CCNA1, MODULE_88, MODULE_203, MODULE_242, SOX5_01, NKX3A_01, WEBER_METHYLATED_HCP_IN_FIBROBLAST_DN, MODULE_104, MODULE_55, OSF2_Q6, GOCC_RIBONUCLEOPROTEIN_COMPLEX

GO Biological Process (1): mRNA splicing, via spliceosome (GO:0000398)

GO Molecular Function (4): mRNA binding (GO:0003729), snRNA binding (GO:0017069), nucleic acid binding (GO:0003676), RNA binding (GO:0003723)

GO Cellular Component (3): nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904), organelle (GO:0043226)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
binding	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1760 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBMXL2	HNRNPC	P07910	728
RBMXL2	HNRNPH1	P31943	724
RBMXL2	TPM3	P06753	644
RBMXL2	HIPK3	Q9H422	618
RBMXL2	HTRA2	O43464	589
RBMXL2	SRSF5	Q13243	586
RBMXL2	KHDRBS1	Q07666	578
RBMXL2	SRSF9	Q13242	562
RBMXL2	TSPY1	P09002	555
RBMXL2	USP9Y	O00507	532
RBMXL2	SMN1	Q16637	529
RBMXL2	TPM1	P09493	524
RBMXL2	DAZ1	Q9NQZ3	514
RBMXL2	KHDRBS3	O75525	481
RBMXL2	USP9X	Q93008	481

IntAct

50 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0915”(physical association)	0.770
YBX1	DDX3X	psi-mi:“MI:0914”(association)	0.610
RBMXL2	RALA	psi-mi:“MI:0915”(physical association)	0.400
	RBMXL2	psi-mi:“MI:0915”(physical association)	0.400
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
ECI2	ARID1A	psi-mi:“MI:0914”(association)	0.350
ECI2	PDLIM1	psi-mi:“MI:0914”(association)	0.350
CDK1	RBMXL2	psi-mi:“MI:0914”(association)	0.350
COQ2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
COX15	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350
DNM1L		psi-mi:“MI:0914”(association)	0.350
HSD17B10	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
SOAT1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
VDAC1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
DLD	EIF3D	psi-mi:“MI:0914”(association)	0.350
HSD17B10	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
DLD	IRS4	psi-mi:“MI:0914”(association)	0.350

BioGRID (40): RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Proximity Label-MS), RBMXL2 (Proximity Label-MS), RBMXL2 (Affinity Capture-MS), RBMXL2 (Affinity Capture-MS)

ESM2 similar proteins: A5A6M3, D4AE41, O22703, O75526, P30352, P35637, P38159, P56959, P60824, P60825, P60826, P62995, P62996, P62997, P78814, P84586, P92965, P92966, Q01560, Q01844, Q14011, Q24491, Q27294, Q28009, Q29RT0, Q3ZBT6, Q4P2Q5, Q4R7F0, Q4R813, Q4V898, Q54Y98, Q55FQ0, Q5RF83, Q61545, Q6IRQ4, Q7ZWA3, Q8L3X8, Q8RWN5, Q8VYA5, Q91VM5

Diamond homologs: A0A0A0LLY1, A0A0D1C8Z4, A5A6M3, C0HFE5, D3Z4I3, D4AE41, M0R7T6, O22703, O35698, O75526, O89086, O93235, P04147, P0C8Z4, P10979, P19682, P19683, P19684, P28644, P38159, P39697, P48809, P49310, P49311, P49313, P49314, P60824, P60825, P60826, P84586, P98179, Q03250, Q03251, Q03878, Q04836, Q05966, Q08473, Q08935, Q08937, Q14011

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Macroautophagy	5	15.2×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	5	41.8×	2e-05
mitophagy	5	37.9×	3e-05
autophagosome assembly	5	26.8×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

38 predictions. Top by Δscore:

Variant	Effect	Δscore
11:7089825:C:A	acceptor_gain	0.5800
11:7089821:C:CA	acceptor_gain	0.5700
11:7089828:A:T	donor_gain	0.5600
11:7089884:G:C	acceptor_gain	0.5100
11:7089823:CCCGG:C	acceptor_gain	0.5000
11:7089827:G:C	acceptor_gain	0.4200
11:7089881:TGAG:T	acceptor_gain	0.3700
11:7089333:C:T	donor_gain	0.3500
11:7089880:TTGAG:T	acceptor_gain	0.3500
11:7089882:G:GC	acceptor_gain	0.3500
11:7089860:GT:G	acceptor_gain	0.3400
11:7089824:CCGG:C	acceptor_gain	0.3100
11:7089849:C:CA	acceptor_gain	0.3100
11:7089849:CGG:C	acceptor_gain	0.3100
11:7090034:G:GT	donor_gain	0.3100
11:7089915:T:TA	donor_gain	0.3000
11:7089927:C:G	donor_gain	0.3000
11:7090031:G:GT	donor_gain	0.3000
11:7089911:G:GT	donor_gain	0.2900
11:7089207:C:T	donor_gain	0.2700
11:7089833:AC:A	acceptor_gain	0.2700
11:7089859:A:AG	acceptor_gain	0.2700
11:7089860:G:GG	acceptor_gain	0.2700
11:7089125:TTG:T	donor_gain	0.2500
11:7089770:G:C	acceptor_gain	0.2500
11:7089741:G:A	acceptor_gain	0.2400
11:7090037:GCCGC:G	donor_gain	0.2400
11:7089343:GATG:G	donor_gain	0.2300
11:7089749:G:A	acceptor_gain	0.2200
11:7089847:TACGG:T	acceptor_gain	0.2200

AlphaMissense

2481 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:7089271:T:C	F51L	1.000
11:7089273:C:A	F51L	1.000
11:7089273:C:G	F51L	1.000
11:7089277:T:C	F53L	1.000
11:7089279:C:A	F53L	1.000
11:7089279:C:G	F53L	1.000
11:7089151:T:C	F11L	0.999
11:7089152:T:C	F11S	0.999
11:7089153:C:A	F11L	0.999
11:7089153:C:G	F11L	0.999
11:7089266:G:C	R49T	0.999
11:7089266:G:T	R49M	0.999
11:7089267:G:C	R49S	0.999
11:7089267:G:T	R49S	0.999
11:7089272:T:C	F51S	0.999
11:7089281:T:A	V54D	0.999
11:7089286:T:C	F56L	0.999
11:7089288:T:A	F56L	0.999
11:7089288:T:G	F56L	0.999
11:7089191:T:A	L24H	0.998
11:7089202:T:C	F28L	0.998
11:7089204:T:A	F28L	0.998
11:7089204:T:G	F28L	0.998
11:7089215:G:T	G32V	0.998
11:7089275:C:A	A52E	0.998
11:7089278:T:C	F53S	0.998
11:7089278:T:G	F53C	0.998
11:7089287:T:C	F56S	0.998
11:7089314:C:A	A65D	0.998
11:7089152:T:G	F11C	0.997

dbSNP variants (sampled 300 via entrez): RS1001028849 (11:7090535 G>T), RS1001460031 (11:7090983 C>A), RS1001837288 (11:7091310 A>C,G,T), RS1003125008 (11:7088967 C>G,T), RS1003451031 (11:7089084 C>A,T), RS1004790682 (11:7091299 T>C), RS1005249901 (11:7091048 C>A,G), RS1005455676 (11:7088914 C>T), RS1005611767 (11:7091606 A>G), RS1005922328 (11:7088710 A>AT), RS1006515476 (11:7089699 A>C), RS1008015657 (11:7087025 C>A), RS1008220578 (11:7087459 T>A), RS1008590277 (11:7088894 A>C,G), RS1008608545 (11:7088382 G>A,C)

Disease associations

OMIM: gene MIM:605444 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

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
bisphenol F	affects cotreatment, decreases methylation	1
bisphenol A	increases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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