RALYL

Summary

RALYL (RALY RNA binding protein like, HGNC:27036) is a protein-coding gene on chromosome 8q21.2, encoding RNA-binding Raly-like protein (Q86SE5).

Enables identical protein binding activity. Located in nucleoplasm.

Source: NCBI Gene 138046 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 55 total — 1 pathogenic
• MANE Select transcript: NM_173848

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27036
Approved symbol	RALYL
Name	RALY RNA binding protein like
Location	8q21.2
Locus type	gene with protein product
Status	Approved
Aliases	HNRPCL3
Ensembl gene	ENSG00000184672
Ensembl biotype	protein_coding
OMIM	614648
Entrez	138046

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000517638, ENST00000517988, ENST00000518065, ENST00000518566, ENST00000521268, ENST00000521376, ENST00000521695, ENST00000522455, ENST00000522613, ENST00000522647, ENST00000523850

RefSeq mRNA: 51 — MANE Select: NM_173848 NM_001100391, NM_001100392, NM_001100393, NM_001287243, NM_001287244, NM_001354305, NM_001354306, NM_001354307, NM_001354308, NM_001354309, NM_001354310, NM_001354311, NM_001354312, NM_001354313, NM_001354314, NM_001354315, NM_001354316, NM_001354317, NM_001354318, NM_001354319, NM_001354320, NM_001354321, NM_001354322, NM_001354323, NM_001354325, NM_001413300, NM_001413301, NM_001413302, NM_001413303, NM_001413304, NM_001413305, NM_001413306, NM_001413307, NM_001413308, NM_001413309, NM_001413310, NM_001413311, NM_001413312, NM_001413313, NM_001413314, NM_001413315, NM_001413316, NM_001413318, NM_001413319, NM_001413320, NM_001413321, NM_001413322, NM_001413323, NM_001413324, NM_001413329, NM_173848

CCDS: CCDS55252, CCDS55253, CCDS75760, CCDS75761

Canonical transcript exons

ENST00000521268 — 9 exons

Exon	Start	End
ENSE00001292637	84849980	84850027
ENSE00001296977	84873284	84873397
ENSE00001309894	84887604	84887776
ENSE00001312341	84862296	84862453
ENSE00001313716	84804770	84804802
ENSE00002107106	84183274	84184424
ENSE00002128105	84774579	84774654
ENSE00003488829	84920894	84921844
ENSE00003800854	84529299	84529577

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 96.42.

FANTOM5 (CAGE): breadth broad, TPM avg 6.0181 / max 538.9551, expressed in 276 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89562	1.6308	131
89588	1.0582	120
89560	0.7284	114
89561	0.3917	96
89567	0.3314	85
89574	0.2562	74
89566	0.2523	81
89569	0.2249	81
89563	0.1904	78
89559	0.1830	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	96.42	gold quality
cerebellar vermis	UBERON:0004720	95.66	gold quality
cortical plate	UBERON:0005343	95.46	gold quality
middle temporal gyrus	UBERON:0002771	95.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.13	gold quality
cerebellar cortex	UBERON:0002129	94.23	gold quality
cerebellar hemisphere	UBERON:0002245	94.21	gold quality
cerebellum	UBERON:0002037	94.18	gold quality
orbitofrontal cortex	UBERON:0004167	93.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.18	gold quality
superior frontal gyrus	UBERON:0002661	93.06	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.00	gold quality
primary visual cortex	UBERON:0002436	92.29	gold quality
prefrontal cortex	UBERON:0000451	92.15	gold quality
hypothalamus	UBERON:0001898	92.15	gold quality
cingulate cortex	UBERON:0003027	92.00	gold quality
anterior cingulate cortex	UBERON:0009835	91.97	gold quality
frontal cortex	UBERON:0001870	91.79	gold quality
neocortex	UBERON:0001950	91.56	gold quality
postcentral gyrus	UBERON:0002581	91.51	gold quality
cerebral cortex	UBERON:0000956	91.32	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.24	gold quality
nucleus accumbens	UBERON:0001882	91.16	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.11	gold quality
parietal lobe	UBERON:0001872	90.90	gold quality
occipital lobe	UBERON:0002021	90.61	gold quality
entorhinal cortex	UBERON:0002728	90.57	gold quality
Brodmann (1909) area 10	UBERON:0013541	90.41	gold quality
telencephalon	UBERON:0001893	90.17	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	3755.08
E-HCAD-35	yes	3567.32
E-HCAD-25	yes	2326.06
E-HCAD-5	yes	42.54
E-CURD-119	yes	32.80
E-GEOD-93593	yes	6.60
E-ANND-3	yes	4.70
E-HCAD-30	no	2814.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting RALYL, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-499A-5P	99.98	70.79	1323
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-3692-3P	99.98	70.27	2139
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AC	99.84	70.77	4351

Literature-anchored findings (GeneRIF, showing 2)

• Exploring the role of RALYL in Alzheimer’s disease reserve by network-based approaches. (PMID:33298176)
• Over-expression of RALYL suppresses the progression of ovarian clear cell carcinoma through inhibiting MAPK and CDH1 signaling pathways. (PMID:33437214)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hnrnpc	ENSDARG00000053810
danio_rerio	zgc:55733	ENSDARG00000103845
mus_musculus	Ralyl	ENSMUSG00000039717
rattus_norvegicus	Ralyl	ENSRNOG00000011400

Paralogs (6): HNRNPC (ENSG00000092199), RALY (ENSG00000125970), HNRNPCL1 (ENSG00000179172), HNRNPCL4 (ENSG00000179412), HNRNPCL2 (ENSG00000275774), HNRNPCL3 (ENSG00000277058)

Protein

Protein identifiers

RNA-binding Raly-like protein — Q86SE5 (reviewed: Q86SE5)

Alternative names: Heterogeneous nuclear ribonucleoprotein C-like 3

All UniProt accessions (5): Q86SE5, B3KT61, E5RG71, E5RIX9, E5RJ39

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Widely expressed, with highest levels in brain.

Similarity. Belongs to the RRM HNRPC family. RALY subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86SE5-1	1	yes
Q86SE5-2	2
Q86SE5-3	3

RefSeq proteins (51): NP_001093861, NP_001093862, NP_001093863, NP_001274172, NP_001274173, NP_001341234, NP_001341235, NP_001341236, NP_001341237, NP_001341238, NP_001341239, NP_001341240, NP_001341241, NP_001341242, NP_001341243, NP_001341244, NP_001341245, NP_001341246, NP_001341247, NP_001341248, NP_001341249, NP_001341250, NP_001341251, NP_001341252, NP_001341254, NP_001400229, NP_001400230, NP_001400231, NP_001400232, NP_001400233, NP_001400234, NP_001400235, NP_001400236, NP_001400237, NP_001400238, NP_001400239, NP_001400240, NP_001400241, NP_001400242, NP_001400243, NP_001400244, NP_001400245, NP_001400247, NP_001400248, NP_001400249, NP_001400250, NP_001400251, NP_001400252, NP_001400253, NP_001400258, NP_776247* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR017347	hnRNP_C	Family
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR051186	RRM_HNRPC/RALY_subfam	Family

Pfam: PF00076

UniProt features (11 total): splice variant 3, region of interest 2, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SE5-F1	71.18	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 136 (showing top): GNF2_RTN1, GCANCTGNY_MYOD_Q6, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, AGTCTTA_MIR499, TCF4_Q5, CDP_01, USF_01, GNF2_TM4SF2, OCT1_06, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, HFH1_01, AACTTT_UNKNOWN, TGGNNNNNNKCCAR_UNKNOWN, USF_02, HAND1E47_01

GO Biological Process (0):

GO Molecular Function (4): RNA binding (GO:0003723), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
nucleic acid binding	1
protein binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RALYL	OR52N5	Q8NH56	711
RALYL	RHCG	Q9UBD6	639
RALYL	RBM22	Q9NW64	566
RALYL	TIGD3	Q6B0B8	547
RALYL	SLC4A1	P02730	525
RALYL	PLPP1	O14494	495
RALYL	UMOD	P07911	489
RALYL	RBIS	Q8N0T1	484
RALYL	RBMXL2	O75526	456
RALYL	LRRCC1	Q9C099	449
RALYL	CA9	Q16790	447
RALYL	HNRNPUL2	Q1KMD3	441
RALYL	HNRNPCL3	B7ZW38	439
RALYL	HNRNPCL1	O60812	432
RALYL	HNRNPCL2	B2RXH8	431

IntAct

58 interactions, top by confidence:

A	B	Type	Score
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
RALYL	HNRNPC	psi-mi:“MI:0915”(physical association)	0.740
HNRNPC	RALYL	psi-mi:“MI:0915”(physical association)	0.740
RBM41	RALYL	psi-mi:“MI:0915”(physical association)	0.670
RALYL	THAP1	psi-mi:“MI:0915”(physical association)	0.670
RALYL	RBM41	psi-mi:“MI:0915”(physical association)	0.670
RALYL	RALYL	psi-mi:“MI:0915”(physical association)	0.670
THAP1	RALYL	psi-mi:“MI:0915”(physical association)	0.670
BYSL	RALYL	psi-mi:“MI:0915”(physical association)	0.560
RALYL	AEN	psi-mi:“MI:0915”(physical association)	0.560
RALYL	BYSL	psi-mi:“MI:0915”(physical association)	0.560
AEN	RALYL	psi-mi:“MI:0915”(physical association)	0.560
RALYL	RALY	psi-mi:“MI:0915”(physical association)	0.560
CEP170P1	RALYL	psi-mi:“MI:0915”(physical association)	0.550
RALYL	FXR2	psi-mi:“MI:0915”(physical association)	0.550
RALYL	CEP170P1	psi-mi:“MI:0915”(physical association)	0.550
FXR2	RALYL	psi-mi:“MI:0915”(physical association)	0.550

BioGRID (144): RALYL (Two-hybrid), RALYL (Two-hybrid), RALYL (Two-hybrid), RALYL (Two-hybrid), RALYL (Two-hybrid), RALYL (Two-hybrid), CCDC9 (Affinity Capture-MS), SKA2 (Affinity Capture-MS), ELAVL2 (Affinity Capture-MS), CRNKL1 (Affinity Capture-MS), SF3A1 (Affinity Capture-MS), RBM22 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), CDC40 (Affinity Capture-MS), PNN (Affinity Capture-MS)

ESM2 similar proteins: A4IGK3, B7ZAP0, O08609, O54941, O55047, O60519, P18847, P26801, P28574, P29596, P37285, P52161, P52162, P52164, P60762, P61244, P61245, P97875, Q07016, Q07866, Q08CW1, Q08DJ0, Q0VCP9, Q0VD32, Q13330, Q28772, Q2KII1, Q32KT0, Q32M00, Q3T0B9, Q56A18, Q5BJU6, Q5R581, Q5ZIL4, Q60765, Q62599, Q642H2, Q6PH81, Q78E65, Q7TMY4

Diamond homologs: B2RXH8, B7ZW38, G3V9R8, O60812, O77768, P07910, P0DMR1, P19600, Q08DJ0, Q0VFL7, Q5RA82, Q64012, Q86SE5, Q8BTF8, Q9UKM9, Q9V3V0, Q9Z204, Q16629, Q3T106, Q8BL97, Q9W4D2, P38996, Q13247, Q29RT0, Q3B7L6, Q9WX39, F4JHI7, O22315, P84103, P84104, Q10145, Q3SZR8, Q74ZS6, Q94901, Q9FYB7, Q9LIS2, Q9XFR5, G3V6S8, Q3TWW8, Q6IQ97

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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.

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	5	15.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	46
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2684546	GRCh37/hg19 8q21.12-22.3(chr8:79046933-102008860)x3	Pathogenic

SpliceAI

3063 predictions. Top by Δscore:

Variant	Effect	Δscore
8:84184999:A:AG	donor_gain	1.0000
8:84185015:G:GG	donor_gain	1.0000
8:84457198:G:GT	donor_gain	1.0000
8:84529283:T:TA	acceptor_gain	1.0000
8:84529287:T:TA	acceptor_gain	1.0000
8:84529291:T:A	acceptor_gain	1.0000
8:84529291:T:TA	acceptor_loss	1.0000
8:84529296:A:AG	acceptor_gain	1.0000
8:84529296:AAG:A	acceptor_gain	1.0000
8:84529297:A:AG	acceptor_gain	1.0000
8:84529297:A:AT	acceptor_loss	1.0000
8:84529297:AG:A	acceptor_gain	1.0000
8:84529298:G:A	acceptor_gain	1.0000
8:84529298:G:GA	acceptor_gain	1.0000
8:84529298:GGA:G	acceptor_gain	1.0000
8:84529298:GGATT:G	acceptor_gain	1.0000
8:84529574:CTTG:C	donor_gain	1.0000
8:84529578:G:C	donor_loss	1.0000
8:84529578:G:GG	donor_gain	1.0000
8:84529579:TAAG:T	donor_loss	1.0000
8:84184952:G:GT	donor_gain	0.9900
8:84184999:A:G	donor_gain	0.9900
8:84185003:G:GG	donor_gain	0.9900
8:84185012:GCA:G	donor_gain	0.9900
8:84234473:GAT:G	donor_gain	0.9900
8:84346151:G:GG	donor_gain	0.9900
8:84393026:G:GT	donor_gain	0.9900
8:84418078:G:GG	donor_gain	0.9900
8:84457165:TTTGG:T	donor_gain	0.9900
8:84484503:G:GT	donor_gain	0.9900

AlphaMissense

1894 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:84529353:C:T	T11I	1.000
8:84529373:T:C	S18P	1.000
8:84529382:T:C	S21P	1.000
8:84529385:C:A	R22S	1.000
8:84529385:C:G	R22G	1.000
8:84529386:G:C	R22P	1.000
8:84529389:T:A	V23D	1.000
8:84529391:T:A	F24I	1.000
8:84529391:T:C	F24L	1.000
8:84529391:T:G	F24V	1.000
8:84529392:T:C	F24S	1.000
8:84529392:T:G	F24C	1.000
8:84529393:C:A	F24L	1.000
8:84529393:C:G	F24L	1.000
8:84529395:T:A	I25N	1.000
8:84529397:G:A	G26S	1.000
8:84529397:G:C	G26R	1.000
8:84529397:G:T	G26C	1.000
8:84529398:G:A	G26D	1.000
8:84529398:G:T	G26V	1.000
8:84529400:A:G	N27D	1.000
8:84529401:A:T	N27I	1.000
8:84529402:T:A	N27K	1.000
8:84529402:T:G	N27K	1.000
8:84529404:T:A	L28Q	1.000
8:84529404:T:C	L28P	1.000
8:84529404:T:G	L28R	1.000
8:84529419:T:A	V33D	1.000
8:84529445:T:A	F42I	1.000
8:84529445:T:C	F42L	1.000

dbSNP variants (sampled 300 via entrez): RS1000000017 (8:84905735 C>T), RS1000001274 (8:84562937 C>T), RS1000001762 (8:84770941 G>A,T), RS1000008286 (8:84484695 A>G), RS1000008702 (8:84730374 G>T), RS1000010200 (8:84729979 T>A), RS1000011142 (8:84572779 G>T), RS1000024152 (8:84722889 A>G), RS1000028888 (8:84196520 A>C), RS1000029218 (8:84183410 T>A), RS1000037885 (8:84366097 G>T), RS1000043786 (8:84421911 G>A,T), RS1000050043 (8:84670789 T>A), RS1000056254 (8:84777677 G>A,T), RS1000057368 (8:84611646 G>A)

Disease associations

OMIM: gene MIM:614648 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002408_5	Response to methotrexate in juvenile idiopathic arthritis	3.000000e-06
GCST002408_6	Response to methotrexate in juvenile idiopathic arthritis	2.000000e-06
GCST002783_261	Body mass index	2.000000e-07
GCST002783_616	Body mass index	5.000000e-08
GCST003542_57	Night sleep phenotypes	4.000000e-06
GCST004904_264	Body mass index	9.000000e-09
GCST005316_87	Intelligence (MTAG)	4.000000e-08
GCST006269_1167	General cognitive ability	3.000000e-08
GCST006269_390	General cognitive ability	2.000000e-10
GCST007094_167	Diastolic blood pressure	4.000000e-10
GCST007099_155	Systolic blood pressure	3.000000e-06
GCST008154_44	Trunk fat mass	5.000000e-06
GCST010988_303	Adult body size	3.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004337	intelligence
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Clozapine	increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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