XTBD1

Summary

XTBD1 (XRN2 binding domain containing 1, HGNC:30545) is a protein-coding gene on chromosome 5q31.1, encoding CDKN2AIP N-terminal-like protein (Q96HQ2).

At a glance

• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_080656

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30545
Approved symbol	XTBD1
Name	XRN2 binding domain containing 1
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC13017, C2AIL
Ensembl gene	ENSG00000237190
Ensembl biotype	protein_coding
Entrez	91368

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000395009, ENST00000458198

RefSeq mRNA: 1 — MANE Select: NM_080656 NM_080656

CCDS: CCDS4175

Canonical transcript exons

ENST00000458198 — 3 exons

Exon	Start	End
ENSE00000972555	134409903	134410002
ENSE00001276178	134411616	134411881
ENSE00001739481	134402065	134402926

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 93.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.2208 / max 235.5822, expressed in 1814 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63460	39.2829	1810
63461	6.9379	1716

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	93.92	gold quality
gastrocnemius	UBERON:0001388	93.14	gold quality
muscle of leg	UBERON:0001383	92.97	gold quality
body of pancreas	UBERON:0001150	91.82	gold quality
prefrontal cortex	UBERON:0000451	91.30	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.27	gold quality
anterior cingulate cortex	UBERON:0009835	91.08	gold quality
cortical plate	UBERON:0005343	90.71	gold quality
right frontal lobe	UBERON:0002810	90.40	gold quality
ganglionic eminence	UBERON:0004023	90.38	gold quality
right atrium auricular region	UBERON:0006631	90.24	gold quality
heart left ventricle	UBERON:0002084	90.13	gold quality
apex of heart	UBERON:0002098	89.83	gold quality
cardiac ventricle	UBERON:0002082	89.31	gold quality
islet of Langerhans	UBERON:0000006	89.23	gold quality
pancreas	UBERON:0001264	89.20	gold quality
cardiac atrium	UBERON:0002081	88.77	gold quality
left adrenal gland cortex	UBERON:0035825	88.73	gold quality
left adrenal gland	UBERON:0001234	88.56	gold quality
right adrenal gland	UBERON:0001233	88.36	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.14	gold quality
cerebellar hemisphere	UBERON:0002245	88.03	gold quality
right adrenal gland cortex	UBERON:0035827	88.03	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.98	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.91	gold quality
heart	UBERON:0000948	87.86	gold quality
cerebellar cortex	UBERON:0002129	87.85	gold quality
mucosa of transverse colon	UBERON:0004991	87.65	gold quality
hypothalamus	UBERON:0001898	87.38	gold quality
adenohypophysis	UBERON:0002196	87.25	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6075	no	419.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting XTBD1, 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-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-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-548AQ-3P	99.93	72.66	4867
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4668-5P	99.79	70.58	3782

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdkn2aipnl	ENSDARG00000053395
mus_musculus	Cdkn2aipnl	ENSMUSG00000020392
rattus_norvegicus	Cdkn2aipnl	ENSRNOG00000005024
drosophila_melanogaster	CG31301	FBGN0051301
caenorhabditis_elegans	paxt-1	WBGENE00011034

Paralogs (2): CDKN2AIP (ENSG00000168564), NKRF (ENSG00000186416)

Protein

Protein identifiers

CDKN2AIP N-terminal-like protein — Q96HQ2 (reviewed: Q96HQ2)

Alternative names: CDKN2A-interacting protein N-terminal-like protein

All UniProt accessions (1): Q96HQ2

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with XRN2; the interaction is direct.

Similarity. Belongs to the CARF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96HQ2-1	1	yes
Q96HQ2-2	2

RefSeq proteins (1): NP_542387* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021859	XTBD	Domain

Pfam: PF11952

UniProt features (5 total): chain 1, domain 1, modified residue 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96HQ2-F1	90.95	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (1):

Position	Phenotype
81	abolishes binding to xrn2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): PATIL_LIVER_CANCER, FISCHER_DREAM_TARGETS, chr5q31, LU_EZH2_TARGETS_DN, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN, DIDO1_TARGET_GENES, HMG20B_TARGET_GENES, NFE2L1_TARGET_GENES, OVOL3_TARGET_GENES, RBM34_TARGET_GENES, SNIP1_TARGET_GENES, ZBTB12_TARGET_GENES, ZNF197_TARGET_GENES, ZNF213_TARGET_GENES, ZNF30_TARGET_GENES

GO Biological Process (0):

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
binding	1

Protein interactions and networks

STRING

312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XTBD1	EPB41L5	Q9HCM4	488
XTBD1	IQCF6	A8MYZ5	447
XTBD1	EID2B	Q96D98	400
XTBD1	SLC61A1	Q6N075	400
XTBD1	C1orf54	Q8WWF1	356
XTBD1	PDCD2L	Q9BRP1	349
XTBD1	TP53I13	Q8NBR0	348
XTBD1	PCED1B	Q96HM7	328
XTBD1	C9JR48	C9JR48	326
XTBD1	ZMYM6	O95789	314
XTBD1	ZCRB1	Q8TBF4	313
XTBD1	ENTR1	Q96C92	312
XTBD1	MIGA1	Q8NAN2	311
XTBD1	VMA22	Q96NT0	305
XTBD1	METTL21A	Q8WXB1	305

IntAct

23 interactions, top by confidence:

A	B	Type	Score
CDKN2AIPNL	XRN2	psi-mi:“MI:0915”(physical association)	0.800
CTAG1A	CDKN2AIPNL	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	CDKN2AIPNL	psi-mi:“MI:0915”(physical association)	0.560
AGR2	CDKN2AIPNL	psi-mi:“MI:0915”(physical association)	0.560
CDKN2AIPNL	KPNA1	psi-mi:“MI:0914”(association)	0.530
xrn2	CDKN2AIPNL	psi-mi:“MI:0407”(direct interaction)	0.440
CDKN2AIPNL	xrn-2	psi-mi:“MI:0915”(physical association)	0.400
espY1	CDKN2AIPNL	psi-mi:“MI:0915”(physical association)	0.370
CDKN2AIPNL	SEC16A	psi-mi:“MI:0914”(association)	0.350
XRN2	NKRF	psi-mi:“MI:0914”(association)	0.350
rl3_rl3l_human	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
CDKN2AIPNL	SPTB	psi-mi:“MI:0914”(association)	0.350
ZNF574	POLRMT	psi-mi:“MI:0914”(association)	0.350
HRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
CDKN2AIPNL	CTAG1A	psi-mi:“MI:0915”(physical association)	0.000
CDKN2AIPNL	AGR2	psi-mi:“MI:0915”(physical association)	0.000
NTAQ1	CDKN2AIPNL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): TAF12 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), SEC16A (Affinity Capture-MS), XRN2 (Affinity Capture-MS), WAC (Affinity Capture-MS), NCKAP5L (Affinity Capture-MS), PSRC1 (Affinity Capture-MS), PLEKHA8 (Affinity Capture-MS), CHAMP1 (Affinity Capture-MS), CDKN2AIPNL (Affinity Capture-MS), CDKN2AIPNL (Two-hybrid), CDKN2AIPNL (Two-hybrid), CDKN2AIPNL (Two-hybrid), CTAG1A (Two-hybrid), CDKN2AIPNL (Affinity Capture-MS)

ESM2 similar proteins: A0A1P8ARG1, A2WXR5, A2XTW9, A2Y0Q2, A2Y4R8, A9RNY0, B1Q3J6, B8ADZ3, B8AMA8, B8B8C5, B8B8I3, B8BJV8, F4JTJ9, F4JYC8, O81488, P34881, P58270, Q0WNP7, Q24JY8, Q2QYR5, Q2R837, Q3TTP0, Q40359, Q40476, Q58DR0, Q5XEM9, Q5YDB5, Q60DW3, Q6EPZ2, Q6H509, Q6IEK5, Q6PI47, Q6YTY3, Q6Z7F4, Q75IR6, Q75LH6, Q7F2Z1, Q7XUW3, Q84TV4, Q8H383

Diamond homologs: Q24JY8, Q5RK03, Q5U2X0, Q6PAV5, Q7ZXV6, Q8BI72, Q96HQ2, Q9D211, Q9NXV6, O15226, Q8BY02

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

377 predictions. Top by Δscore:

Variant	Effect	Δscore
5:134402925:TG:T	acceptor_gain	1.0000
5:134402927:C:CC	acceptor_gain	1.0000
5:134409898:TTTA:T	donor_loss	0.9900
5:134409899:TTA:T	donor_loss	0.9900
5:134409900:TA:T	donor_loss	0.9900
5:134409901:A:AG	donor_loss	0.9900
5:134409998:TGTAA:T	acceptor_gain	0.9900
5:134409999:GTAA:G	acceptor_gain	0.9900
5:134410000:TAA:T	acceptor_gain	0.9900
5:134410001:AACT:A	acceptor_loss	0.9900
5:134410002:AC:A	acceptor_loss	0.9900
5:134410003:C:CA	acceptor_loss	0.9900
5:134410003:C:CC	acceptor_gain	0.9900
5:134410004:T:C	acceptor_loss	0.9900
5:134410907:T:TA	donor_gain	0.9900
5:134402924:ATGC:A	acceptor_loss	0.9800
5:134402926:GC:G	acceptor_loss	0.9800
5:134402927:CTGGG:C	acceptor_loss	0.9800
5:134402928:T:A	acceptor_loss	0.9800
5:134410001:AA:A	acceptor_gain	0.9800
5:134410006:C:CT	acceptor_gain	0.9800
5:134402924:A:C	acceptor_gain	0.9700
5:134409921:T:TA	donor_gain	0.9700
5:134410997:TTGAG:T	donor_gain	0.9700
5:134402922:TGATG:T	acceptor_gain	0.9600
5:134402923:GATG:G	acceptor_gain	0.9600
5:134410937:T:C	donor_gain	0.9600
5:134411743:T:TA	donor_gain	0.9600
5:134411645:G:T	donor_gain	0.9500
5:134402924:A:AC	acceptor_gain	0.9400

AlphaMissense

768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:134411627:G:C	F76L	0.998
5:134411627:G:T	F76L	0.998
5:134411629:A:G	F76L	0.998
5:134411726:G:C	F43L	0.998
5:134411726:G:T	F43L	0.998
5:134411727:A:G	F43S	0.998
5:134411728:A:G	F43L	0.998
5:134411628:A:G	F76S	0.996
5:134411644:A:G	W71R	0.996
5:134411644:A:T	W71R	0.996
5:134411652:G:A	S68F	0.996
5:134411744:C:A	W37C	0.996
5:134411744:C:G	W37C	0.996
5:134409930:A:C	F104L	0.995
5:134409930:A:T	F104L	0.995
5:134409932:A:G	F104L	0.995
5:134410001:A:G	Y81H	0.995
5:134411642:C:A	W71C	0.995
5:134411642:C:G	W71C	0.995
5:134411737:G:T	R40S	0.995
5:134411746:A:G	W37R	0.995
5:134411746:A:T	W37R	0.995
5:134411622:C:A	G78V	0.994
5:134411622:C:T	G78D	0.994
5:134411646:A:T	V70D	0.993
5:134411727:A:C	F43C	0.993
5:134409965:C:G	A93P	0.992
5:134409967:A:G	M92T	0.992
5:134409988:A:G	L85P	0.992
5:134411629:A:T	F76I	0.992

dbSNP variants (sampled 300 via entrez): RS1001308979 (5:134412012 C>CGGCTCCT), RS1002021217 (5:134411500 G>A,C,T), RS1002172185 (5:134406509 G>A), RS1002248581 (5:134404058 G>A,C,T), RS1002321613 (5:134413333 T>C), RS1002631340 (5:134406111 G>A,C), RS1002775449 (5:134401947 A>G,T), RS1002840264 (5:134409541 G>A), RS1003227325 (5:134407815 G>A,C), RS1003585831 (5:134408112 C>G), RS1003699183 (5:134409718 C>A,G), RS1003804708 (5:134407494 C>T), RS1004254581 (5:134411412 C>T), RS1005111526 (5:134408799 G>A), RS1005125380 (5:134403647 C>T)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	5
bisphenol A	decreases expression	2
chloropicrin	increases expression	2
Formaldehyde	decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
arsenite	increases reaction, affects binding	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	increases abundance, increases expression	1
avobenzone	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	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	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Hydrogen Peroxide	increases expression	1
Lead	increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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