IFRD2

Summary

IFRD2 (interferon related developmental regulator 2, HGNC:5457) is a protein-coding gene on chromosome 3p21.31, encoding Interferon-related developmental regulator 2 (Q12894). Ribosome-binding protein that acts as an inhibitor of mRNA translation by promoting ribosome inactivation.

Enables ribosome binding activity and translation repressor activity. Involved in negative regulation of translation. Located in nucleus.

Source: NCBI Gene 7866 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 117 total
• MANE Select transcript: NM_006764

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5457
Approved symbol	IFRD2
Name	interferon related developmental regulator 2
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	SKMc15, SM15, IFNRP
Ensembl gene	ENSG00000214706
Ensembl biotype	protein_coding
OMIM	602725
Entrez	7866

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 16 protein_coding, 8 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000414734, ENST00000417626, ENST00000426499, ENST00000436390, ENST00000438296, ENST00000462001, ENST00000464258, ENST00000468737, ENST00000469855, ENST00000474556, ENST00000483071, ENST00000484043, ENST00000486322, ENST00000489569, ENST00000492387, ENST00000879008, ENST00000879009, ENST00000879010, ENST00000879011, ENST00000879012, ENST00000879013, ENST00000879014, ENST00000921977, ENST00000948686, ENST00000948687, ENST00000948688, ENST00000948689, ENST00000948690

RefSeq mRNA: 1 — MANE Select: NM_006764 NM_006764

CCDS: CCDS77746

Canonical transcript exons

ENST00000417626 — 12 exons

Exon	Start	End
ENSE00001651299	50292217	50292429
ENSE00001810711	50287732	50288271
ENSE00003479960	50288409	50288504
ENSE00003480342	50288800	50288937
ENSE00003480517	50290560	50290679
ENSE00003497156	50289447	50289628
ENSE00003538278	50289929	50290086
ENSE00003571428	50290170	50290294
ENSE00003579449	50288583	50288711
ENSE00003606359	50290388	50290472
ENSE00003611544	50289712	50289762
ENSE00003647278	50289255	50289360

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 97.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.0218 / max 232.4783, expressed in 1793 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42303	14.3470	1776
42302	5.7745	1524
42300	1.2223	678
42301	0.4150	220
42299	0.2381	89
42304	0.0249	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.70	gold quality
body of stomach	UBERON:0001161	97.09	gold quality
gastrocnemius	UBERON:0001388	96.87	gold quality
right lobe of liver	UBERON:0001114	96.78	gold quality
apex of heart	UBERON:0002098	96.70	gold quality
lower esophagus mucosa	UBERON:0035834	96.69	gold quality
mucosa of transverse colon	UBERON:0004991	96.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.18	gold quality
muscle of leg	UBERON:0001383	96.04	gold quality
right lobe of thyroid gland	UBERON:0001119	95.65	gold quality
stomach	UBERON:0000945	95.48	gold quality
left uterine tube	UBERON:0001303	95.39	gold quality
left lobe of thyroid gland	UBERON:0001120	95.29	gold quality
muscle organ	UBERON:0001630	95.19	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.00	gold quality
minor salivary gland	UBERON:0001830	94.95	gold quality
metanephros cortex	UBERON:0010533	94.91	gold quality
lower esophagus	UBERON:0013473	94.89	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.89	gold quality
heart left ventricle	UBERON:0002084	94.86	gold quality
cardiac ventricle	UBERON:0002082	94.65	gold quality
omental fat pad	UBERON:0010414	94.61	gold quality
peritoneum	UBERON:0002358	94.57	gold quality
transverse colon	UBERON:0001157	94.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.46	gold quality
right atrium auricular region	UBERON:0006631	94.44	gold quality
esophagus mucosa	UBERON:0002469	94.41	gold quality
esophagus	UBERON:0001043	94.39	gold quality
thyroid gland	UBERON:0002046	94.24	gold quality
upper lobe of left lung	UBERON:0008952	94.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

22 targeting IFRD2, 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-6876-5P	100.00	67.68	2126
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-34A-3P	96.80	67.70	805

Literature-anchored findings (GeneRIF, showing 3)

• Identification of a new family of IFRD (interferon developmental regulator) genes, of which SkMC15 is part, being named IFDR2 (PMID:9722946)
• Identification of the IFRD gene family, comprising the two genes PC4 / Tis7 / IFRD1 and SKMc15 / IFRD2, and in situ-hybridization analysis of their expression during developments (PMID:9722946)
• This publication discusses both IFRD1 and IFRD2. (PMID:9722946)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ifrd2	ENSDARG00000036811
mus_musculus	Ifrd2	ENSMUSG00000010048
rattus_norvegicus	Ifrd2	ENSRNOG00000016150
drosophila_melanogaster	Ifrd1	FBGN0051694
caenorhabditis_elegans		WBGENE00010232

Paralogs (1): IFRD1 (ENSG00000006652)

Protein

Protein identifiers

Interferon-related developmental regulator 2 — Q12894 (reviewed: Q12894)

Alternative names: Protein SKMC15

All UniProt accessions (4): Q12894, F8WEI6, H7C2Z4, H7C444

UniProt curated annotations — full annotation on UniProt →

Function. Ribosome-binding protein that acts as an inhibitor of mRNA translation by promoting ribosome inactivation. Associates with the P- and E-sites of the ribosome and inserts a C-terminal helix into the mRNA exit channel to preclude translation.

Subunit / interactions. Associates with ribosomes; promoting ribosome inactivation.

Tissue specificity. Expressed in many tissues including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Similarity. Belongs to the IFRD family.

RefSeq proteins (1): NP_006755* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006921	Interferon-rel_develop_reg_C	Domain
IPR007701	Interferon-rel_develop_reg_N	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR039777	IFRD	Family

Pfam: PF04836, PF05004

UniProt features (5 total): compositionally biased region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12894-F1	85.96	0.73

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 227 (showing top): FXR_IR1_Q6, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, LFA1_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, AACYNNNNTTCCS_UNKNOWN, MODULE_16, SHIPP_DLBCL_CURED_VS_FATAL_DN, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, MCAATNNNNNGCG_UNKNOWN

GO Biological Process (5): Wnt signaling pathway (GO:0016055), negative regulation of translation (GO:0017148), fat cell differentiation (GO:0045444), adipose tissue development (GO:0060612), regulation of translation (GO:0006417)

GO Molecular Function (3): translation repressor activity (GO:0030371), ribosome binding (GO:0043022), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	2
cell surface receptor signaling pathway	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
cell differentiation	1
animal organ development	1
connective tissue development	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
negative regulation of translation	1
translation regulator activity	1
ribonucleoprotein complex binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFRD2	NDC80	O14777	525
IFRD2	SERBP1	Q8NC51	510
IFRD2	CCDC124	Q96CT7	508
IFRD2	ARHGEF38	Q9NXL2	488
IFRD2	GFM2	Q969S9	467
IFRD2	OSBPL9	Q96SU4	446
IFRD2	SIN3B	O75182	425
IFRD2	SH3RF1	Q7Z6J0	422
IFRD2	IRF2BP1	Q8IU81	421
IFRD2	PTDSS1	P48651	421
IFRD2	KHDRBS2	Q5VWX1	420
IFRD2	OSBPL8	Q9BZF1	415
IFRD2	QDPR	P09417	414
IFRD2	WDR36	Q8NI36	414
IFRD2	CNTN3	Q9P232	413

IntAct

38 interactions, top by confidence:

A	B	Type	Score
IFRD2	UBE2O	psi-mi:“MI:0915”(physical association)	0.620
IFRD2	MDFI	psi-mi:“MI:0915”(physical association)	0.560
JRK	IFRD2	psi-mi:“MI:0915”(physical association)	0.560
IFRD2	EIF3J	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IFRD2	OAS3	psi-mi:“MI:0915”(physical association)	0.500
	IFRD2	psi-mi:“MI:0407”(direct interaction)	0.440
E2F8	IFRD2	psi-mi:“MI:0915”(physical association)	0.400
Hacd3	IFRD2	psi-mi:“MI:0915”(physical association)	0.400
PSMD2	IFRD2	psi-mi:“MI:0915”(physical association)	0.400
Usp19	IFRD2	psi-mi:“MI:0915”(physical association)	0.400
AARSD1	IFRD2	psi-mi:“MI:0915”(physical association)	0.400
IFRD2	POT1	psi-mi:“MI:0915”(physical association)	0.370
IFRD2	E7	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Cd2ap		psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
HDAC6	GLOD5	psi-mi:“MI:0914”(association)	0.350
NPM1	RPSA	psi-mi:“MI:0914”(association)	0.350
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
USP36	STK25	psi-mi:“MI:0914”(association)	0.350
G3BP1	HAT1	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
OAS3	PPM1G	psi-mi:“MI:0914”(association)	0.350
CD40	IPO5	psi-mi:“MI:0914”(association)	0.350
EPHA1	ENC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): IFRD2 (Affinity Capture-RNA), IFRD2 (Affinity Capture-RNA), IFRD2 (Affinity Capture-RNA), IFRD2 (Co-fractionation), NOP58 (Co-fractionation), IFRD2 (Affinity Capture-MS), IFRD2 (Affinity Capture-MS), IFRD2 (Affinity Capture-MS), IFRD2 (Affinity Capture-MS), IFRD2 (Affinity Capture-MS), UBE2O (Affinity Capture-MS), EIF3J (Affinity Capture-MS), IFRD2 (Affinity Capture-MS), IFRD2 (Affinity Capture-MS), IFRD2 (Two-hybrid)

ESM2 similar proteins: A1L188, A2AMZ4, A2XK00, A7YY73, B4FGS2, B4FTR7, B8B624, C0HAV3, C5E268, G2TRP6, O13973, O75012, O95159, O95872, Q0VDN7, Q12894, Q28H71, Q2YDD3, Q3SZA2, Q3SZW4, Q3U0S6, Q3UJV1, Q49AH0, Q4G012, Q5FVV3, Q5U509, Q5U651, Q61858, Q6ASS9, Q6P0I6, Q756Q5, Q7S4Y4, Q7XAM0, Q7XK12, Q8BGD8, Q8BGX2, Q8CC36, Q8VED2, Q96BP2, Q96C34

Diamond homologs: O00458, P0DX19, P19182, P20695, Q12894, Q5S1U6, Q9D8U0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	93
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1522 predictions. Top by Δscore:

Variant	Effect	Δscore
3:50288270:TG:T	acceptor_gain	1.0000
3:50288272:C:CC	acceptor_gain	1.0000
3:50288405:AAACC:A	donor_loss	1.0000
3:50288408:C:CA	donor_loss	1.0000
3:50288500:TTGTT:T	acceptor_gain	1.0000
3:50288505:C:CC	acceptor_gain	1.0000
3:50288579:GCAC:G	donor_loss	1.0000
3:50288580:CACCT:C	donor_loss	1.0000
3:50288581:ACCTG:A	donor_loss	1.0000
3:50288582:C:A	donor_loss	1.0000
3:50288601:G:A	donor_gain	1.0000
3:50288617:T:A	donor_gain	1.0000
3:50288617:T:TA	donor_loss	1.0000
3:50288707:CCGCC:C	acceptor_gain	1.0000
3:50288708:CGCCC:C	acceptor_gain	1.0000
3:50288710:CC:C	acceptor_gain	1.0000
3:50288710:CCCT:C	acceptor_loss	1.0000
3:50288711:CC:C	acceptor_gain	1.0000
3:50288711:CCTGC:C	acceptor_loss	1.0000
3:50288712:C:CC	acceptor_gain	1.0000
3:50288712:CTGC:C	acceptor_loss	1.0000
3:50288713:T:G	acceptor_loss	1.0000
3:50288719:G:GC	acceptor_gain	1.0000
3:50288793:CACA:C	donor_gain	1.0000
3:50288801:T:TA	donor_gain	1.0000
3:50288934:CCTC:C	acceptor_gain	1.0000
3:50288935:CTC:C	acceptor_gain	1.0000
3:50288935:CTCC:C	acceptor_gain	1.0000
3:50288936:TCCT:T	acceptor_gain	1.0000
3:50288938:C:CC	acceptor_gain	1.0000

AlphaMissense

3242 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:50288846:C:G	R390P	0.994
3:50288854:C:A	K387N	0.994
3:50288854:C:G	K387N	0.994
3:50288882:G:T	A378D	0.994
3:50288883:C:G	A378P	0.994
3:50288825:A:G	F397S	0.993
3:50288866:C:A	K383N	0.993
3:50288866:C:G	K383N	0.993
3:50289298:C:T	G345D	0.993
3:50288245:T:A	K489N	0.992
3:50288245:T:G	K489N	0.992
3:50288847:G:T	R390S	0.992
3:50288489:G:T	R454S	0.991
3:50288822:C:G	R398P	0.991
3:50288836:C:A	Q393H	0.991
3:50288836:C:G	Q393H	0.991
3:50288835:G:T	R394S	0.990
3:50288868:T:C	K383E	0.990
3:50288823:G:T	R398S	0.989
3:50289286:G:T	A349E	0.989
3:50288824:G:C	F397L	0.988
3:50288824:G:T	F397L	0.988
3:50288826:A:G	F397L	0.988
3:50288834:C:G	R394P	0.988
3:50288587:A:G	L447P	0.987
3:50289299:C:G	G345R	0.987
3:50289502:A:G	W306R	0.987
3:50289502:A:T	W306R	0.987
3:50288237:G:A	T492I	0.985
3:50288244:C:G	A490P	0.985

dbSNP variants (sampled 300 via entrez): RS1002294456 (3:50294356 C>G), RS1002747349 (3:50288424 A>T), RS1003106244 (3:50290829 T>C,G), RS1003484589 (3:50290567 G>A), RS1004079262 (3:50292120 G>A,T), RS1005471533 (3:50289025 G>C), RS1005608719 (3:50289237 C>A,G,T), RS1006448494 (3:50293563 G>C), RS1006828169 (3:50293348 G>A), RS1007138466 (3:50290010 A>C,G), RS1010032172 (3:50287566 G>C,T), RS1010347616 (3:50292925 G>A,T), RS1010488543 (3:50292662 T>A,C,G), RS1010706731 (3:50289900 A>G), RS1013010561 (3:50290928 C>A,T)

Disease associations

OMIM: gene MIM:602725 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST004611_25	High light scatter reticulocyte count	8.000000e-164
GCST004612_59	High light scatter reticulocyte percentage of red cells	3.000000e-162
GCST004619_182	Reticulocyte fraction of red cells	6.000000e-139
GCST004622_160	Reticulocyte count	1.000000e-137
GCST004628_61	Immature fraction of reticulocytes	5.000000e-106
GCST005951_49	Body mass index	1.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST90002385_427	High light scatter reticulocyte count	1.000000e-23
GCST90002385_428	High light scatter reticulocyte count	3.000000e-20
GCST90002385_429	High light scatter reticulocyte count	3.000000e-228
GCST90002386_545	High light scatter reticulocyte percentage of red cells	9.000000e-45
GCST90002386_548	High light scatter reticulocyte percentage of red cells	5.000000e-24
GCST90002386_549	High light scatter reticulocyte percentage of red cells	1.000000e-19
GCST90002386_550	High light scatter reticulocyte percentage of red cells	7.000000e-214
GCST90002387_71	Immature fraction of reticulocytes	4.000000e-30
GCST90002387_74	Immature fraction of reticulocytes	4.000000e-17
GCST90002387_75	Immature fraction of reticulocytes	1.000000e-244
GCST90002396_195	Mean reticulocyte volume	1.000000e-56
GCST90002405_15	Reticulocyte count	7.000000e-17
GCST90002405_16	Reticulocyte count	9.000000e-16
GCST90002405_17	Reticulocyte count	5.000000e-209
GCST90002406_34	Reticulocyte fraction of red cells	6.000000e-18
GCST90002406_35	Reticulocyte fraction of red cells	4.000000e-16
GCST90002406_36	Reticulocyte fraction of red cells	3.000000e-191

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004340	body mass index
EFO:0004346	neuroimaging measurement
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	3
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Nickel	increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Tretinoin	decreases expression	2
Cyclosporine	increases expression	2
daidzein	increases expression, affects cotreatment	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
uranyl acetate	affects expression	1
glycidyl methacrylate	increases expression	1
methylselenic acid	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
glycitein	increases expression, affects cotreatment	1
perfluoro-n-nonanoic acid	increases expression	1
deguelin	increases expression	1
pyrimidifen	increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
pyrachlostrobin	increases expression	1
jinfukang	increases expression	1
picoxystrobin	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1

Clinical trials (associated diseases)

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