C21orf91

Summary

C21orf91 (chromosome 21 open reading frame 91, HGNC:16459) is a protein-coding gene on chromosome 21q21.1, encoding Protein EURL homolog (Q9NYK6). Plays a role in cortical progenitor cell proliferation and differentiation.

Predicted to be involved in cerebral cortex neuron differentiation and positive regulation of dendritic spine development.

Source: NCBI Gene 54149 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_001100420

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16459
Approved symbol	C21orf91
Name	chromosome 21 open reading frame 91
Location	21q21.1
Locus type	gene with protein product
Status	Approved
Aliases	YG81, EURL, CSSG1, BTG3-7:1
Ensembl gene	ENSG00000154642
Ensembl biotype	protein_coding
Entrez	54149

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000284881, ENST00000400558, ENST00000400559, ENST00000405964, ENST00000482915, ENST00000493464, ENST00000908059, ENST00000925071

RefSeq mRNA: 3 — MANE Select: NM_001100420 NM_001100420, NM_001100421, NM_017447

CCDS: CCDS42907, CCDS42908, CCDS42909

Canonical transcript exons

ENST00000284881 — 5 exons

Exon	Start	End
ENSE00001642880	17796582	17797118
ENSE00001934909	17788974	17793581
ENSE00003679576	17818192	17818325
ENSE00003784853	17795208	17795270
ENSE00003845851	17819303	17819356

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 97.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.8936 / max 394.0015, expressed in 1751 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189859	17.7507	1723
189858	0.9737	435
189860	0.9579	672
189861	0.8469	551
189862	0.3643	188

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.90	gold quality
inferior vagus X ganglion	UBERON:0005363	97.31	gold quality
gingival epithelium	UBERON:0001949	97.01	gold quality
palpebral conjunctiva	UBERON:0001812	96.85	gold quality
upper leg skin	UBERON:0004262	96.80	gold quality
corpus callosum	UBERON:0002336	96.29	gold quality
parietal pleura	UBERON:0002400	95.96	gold quality
endothelial cell	CL:0000115	95.89	gold quality
skin of hip	UBERON:0001554	95.89	gold quality
subthalamic nucleus	UBERON:0001906	95.87	gold quality
gingiva	UBERON:0001828	95.80	gold quality
esophagus squamous epithelium	UBERON:0006920	95.59	gold quality
male germ cell	CL:0000015	95.42	gold quality
medial globus pallidus	UBERON:0002477	95.33	gold quality
globus pallidus	UBERON:0001875	95.26	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.92	gold quality
tibia	UBERON:0000979	94.68	gold quality
eye	UBERON:0000970	94.49	gold quality
amniotic fluid	UBERON:0000173	94.26	gold quality
epithelium of nasopharynx	UBERON:0001951	94.21	gold quality
nasopharynx	UBERON:0001728	94.19	gold quality
pleura	UBERON:0000977	93.84	gold quality
visceral pleura	UBERON:0002401	93.65	gold quality
lateral globus pallidus	UBERON:0002476	93.56	gold quality
pons	UBERON:0000988	93.46	gold quality
superior vestibular nucleus	UBERON:0007227	93.44	gold quality
germinal epithelium of ovary	UBERON:0001304	93.33	gold quality
substantia nigra pars compacta	UBERON:0001965	92.07	gold quality
secondary oocyte	CL:0000655	91.30	gold quality
ventral tegmental area	UBERON:0002691	91.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	631.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

269 targeting C21orf91, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-4262	100.00	73.26	3931
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-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960

Literature-anchored findings (GeneRIF, showing 3)

• Authors demonstrate that human AL109761 is in fact the human ortholog of chicken EURL (GeneID: 395489) (PMID:12815627)
• Two complementary techniques identified C21orf91 as a gene of interest for susceptibility to herpes simplex labialis. (PMID:22039568)
• EURL is an important new player in neuronal development that is likely to impact on the neuropathogenesis of HSA21-related disorders including Down Syndrome. (PMID:27404227)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	C10H21orf91	ENSDARG00000030803
mus_musculus	D16Ertd472e	ENSMUSG00000022864
rattus_norvegicus	C11h21orf91	ENSRNOG00000001554

Protein

Protein identifiers

Protein EURL homolog — Q9NYK6 (reviewed: Q9NYK6)

All UniProt accessions (2): Q9NYK6, E7ETB0

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in cortical progenitor cell proliferation and differentiation. Promotes dendritic spine development of post-migratory cortical projection neurons by modulating the beta-catenin signaling pathway.

Subunit / interactions. Interacts with CCDC85B.

Tissue specificity. Expressed in the brain. Expressed in cortical cells of the germinal ventricular zone and the cortical plate. Underexpressed in the dorsolateral prefrontal cortex, primary visual cortex and cerebellar cortex compared with Down Syndrome patients (at protein level).

Similarity. Belongs to the EURL family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NYK6-1	1	yes
Q9NYK6-2	2
Q9NYK6-3	3

RefSeq proteins (3): NP_001093890, NP_001093891, NP_059143 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009704	EURL_prot	Family

Pfam: PF06937

UniProt features (15 total): sequence variant 5, sequence conflict 4, splice variant 2, chain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYK6-F1	65.27	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 246 (showing top): GOBP_DENDRITE_DEVELOPMENT, HORIUCHI_WTAP_TARGETS_DN, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_NEUROGENESIS, USF_C, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_FOREBRAIN_GENERATION_OF_NEURONS, GOBP_CEREBRAL_CORTEX_NEURON_DIFFERENTIATION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_REGULATION_OF_DENDRITIC_SPINE_DEVELOPMENT, TGTGTGA_MIR377, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, GOBP_HEAD_DEVELOPMENT, AACTTT_UNKNOWN

GO Biological Process (4): cerebral cortex neuron differentiation (GO:0021895), positive regulation of dendritic spine development (GO:0060999), nervous system development (GO:0007399), cell differentiation (GO:0030154)

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
forebrain neuron differentiation	1
positive regulation of developmental process	1
dendritic spine development	1
regulation of dendritic spine development	1
system development	1
cellular developmental process	1
binding	1

Protein interactions and networks

STRING

328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C21orf91	RLF	Q13129	466
C21orf91	NEURL1	O76050	441
C21orf91	EOLA2	Q96DE9	432
C21orf91	ARRDC3	Q96B67	407
C21orf91	UFC1	Q9Y3C8	406
C21orf91	BTG3	Q14201	392
C21orf91	TRIM23	P36406	388
C21orf91	ADGRV1	Q8WXG9	356
C21orf91	SLC25A21	Q9BQT8	356
C21orf91	UAP1	Q16222	353
C21orf91	NEURL1B	A8MQ27	351
C21orf91	PABIR2	Q7Z309	350
C21orf91	C8orf58	Q8NAV2	348
C21orf91	TMEM143	Q96AN5	340
C21orf91	DNAJC14	Q6Y2X3	339

IntAct

7 interactions, top by confidence:

A	B	Type	Score
Eurl	SSBP1	psi-mi:“MI:0915”(physical association)	0.400
CCDC85B	EURL	psi-mi:“MI:0915”(physical association)	0.370
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
SCOC	SNAPIN	psi-mi:“MI:0914”(association)	0.350
EURL	GRB2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): C21orf91 (Two-hybrid), C21orf91 (Affinity Capture-MS), C21orf91 (Affinity Capture-MS), C21orf91 (Affinity Capture-MS), C21orf91 (Affinity Capture-MS), C21orf91 (Two-hybrid), C21orf91 (Two-hybrid), C21orf91 (Two-hybrid), C21orf91 (Two-hybrid), C21orf91 (Two-hybrid), C21orf91 (Two-hybrid), C21orf91 (Two-hybrid), C21orf91 (Affinity Capture-RNA), C21orf91 (Affinity Capture-MS), C21orf91 (Affinity Capture-MS)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A2AGB2, A2ALV5, A3KMW7, A6NM62, A8MT70, A9JRX0, D3Z987, P15975, P56716, P70347, Q0P5X5, Q0VET5, Q28FY7, Q2M2Z5, Q3MHT3, Q3U0P1, Q3U3V8, Q3UXL4, Q3V089, Q5SXH7, Q5T1N1, Q5T4T6, Q5VXU9, Q68CR7, Q6NZK5, Q6P2D8, Q7M6U3, Q7Z4H7, Q7Z572, Q7ZYI3, Q7ZZH7, Q80VP2, Q86T90, Q86YC2, Q8BG34, Q8BL06, Q8CCC3, Q8MJ03

Diamond homologs: Q503Y8, Q9D7G4, Q9I8W6, Q9NYK6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1160 predictions. Top by Δscore:

Variant	Effect	Δscore
21:17793579:CTT:C	acceptor_gain	1.0000
21:17793582:C:CC	acceptor_gain	1.0000
21:17795206:AC:A	donor_gain	1.0000
21:17795207:CC:C	donor_gain	1.0000
21:17795267:TTCA:T	acceptor_gain	1.0000
21:17795269:CA:C	acceptor_gain	1.0000
21:17795271:C:CC	acceptor_gain	1.0000
21:17796578:TTA:T	donor_loss	1.0000
21:17796579:TA:T	donor_loss	1.0000
21:17796580:A:AC	donor_gain	1.0000
21:17796580:ACA:A	donor_loss	1.0000
21:17796580:ACATT:A	donor_gain	1.0000
21:17796581:C:CC	donor_gain	1.0000
21:17796581:CATT:C	donor_gain	1.0000
21:17796581:CATTC:C	donor_gain	1.0000
21:17796584:T:A	donor_gain	1.0000
21:17797117:CCCTA:C	acceptor_gain	1.0000
21:17818190:AC:A	donor_gain	1.0000
21:17818191:CC:C	donor_gain	1.0000
21:17818204:G:C	donor_gain	1.0000
21:17793461:TGCAG:T	donor_gain	0.9900
21:17793580:TT:T	acceptor_gain	0.9900
21:17795202:TCTTA:T	donor_loss	0.9900
21:17795203:CTTA:C	donor_loss	0.9900
21:17795204:TTA:T	donor_loss	0.9900
21:17795205:TA:T	donor_loss	0.9900
21:17795206:A:AC	donor_gain	0.9900
21:17795206:A:AT	donor_loss	0.9900
21:17795207:C:CC	donor_gain	0.9900
21:17795267:TTCAC:T	acceptor_loss	0.9900

AlphaMissense

1986 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:17818222:A:G	C33R	0.995
21:17818211:A:C	C36W	0.994
21:17818213:A:G	C36R	0.994
21:17818258:A:G	C21R	0.994
21:17818267:A:G	C18R	0.994
21:17818298:A:C	F7L	0.993
21:17818298:A:T	F7L	0.993
21:17818300:A:G	F7L	0.993
21:17818220:G:C	C33W	0.992
21:17797065:A:G	C61R	0.991
21:17818265:G:C	C18W	0.991
21:17793494:A:G	L272P	0.990
21:17797063:G:C	C61W	0.990
21:17818221:C:T	C33Y	0.990
21:17818223:G:C	F32L	0.990
21:17818223:G:T	F32L	0.990
21:17818225:A:G	F32L	0.990
21:17818212:C:T	C36Y	0.989
21:17818256:A:C	C21W	0.989
21:17818257:C:G	C21S	0.989
21:17818258:A:T	C21S	0.989
21:17818257:C:T	C21Y	0.987
21:17818266:C:G	C18S	0.987
21:17818267:A:T	C18S	0.987
21:17818284:A:G	L12S	0.987
21:17797061:A:G	F62S	0.986
21:17797060:A:C	F62L	0.985
21:17797060:A:T	F62L	0.985
21:17797062:A:G	F62L	0.985
21:17797077:C:G	G57R	0.985

dbSNP variants (sampled 300 via entrez): RS1000002166 (21:17799410 T>C), RS1000316211 (21:17811950 T>C), RS1000348211 (21:17792743 T>C), RS1000593080 (21:17806794 C>G,T), RS1000597309 (21:17800796 C>T), RS1000656538 (21:17810441 T>C), RS1000657601 (21:17801700 G>C,T), RS1000684591 (21:17810062 G>T), RS1000759750 (21:17813366 G>T), RS1000863955 (21:17817348 G>A,C), RS1000953838 (21:17818278 T>A,C), RS1001384921 (21:17797274 T>C), RS1001441180 (21:17790876 A>C), RS1001464743 (21:17790805 G>A), RS1001493931 (21:17802536 T>A,C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST009391_293	Metabolite levels	3.000000e-06
GCST009391_300	Metabolite levels	2.000000e-07
GCST009391_347	Metabolite levels	5.000000e-07
GCST009391_370	Metabolite levels	1.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010425	triacylglycerol 54:7 measurement
EFO:0010426	triacylglycerol 54:8 measurement
EFO:0010432	triacylglycerol 56:5 measurement
EFO:0010436	triacylglycerol 56:9 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	4
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Doxorubicin	affects expression, decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Valproic Acid	decreases expression, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	decreases expression	1
abrine	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
NSC 689534	affects binding, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Amiodarone	increases expression	1
Copper	affects binding, increases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Plant Oils	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Vanadates	increases expression	1
Zinc	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

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