AARD

Summary

AARD (alanine and arginine rich domain containing protein, HGNC:33842) is a protein-coding gene on chromosome 8q24.11, encoding Alanine- and arginine-rich domain-containing protein (Q4LEZ3).

Predicted to act upstream of or within response to testosterone.

Source: NCBI Gene 441376 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 63 total — 30 pathogenic
• MANE Select transcript: NM_001025357

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33842
Approved symbol	AARD
Name	alanine and arginine rich domain containing protein
Location	8q24.11
Locus type	gene with protein product
Status	Approved
Aliases	LOC441376
Ensembl gene	ENSG00000205002
Ensembl biotype	protein_coding
OMIM	621042
Entrez	441376

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000378279, ENST00000523536

RefSeq mRNA: 1 — MANE Select: NM_001025357 NM_001025357

CCDS: CCDS34935

Canonical transcript exons

ENST00000378279 — 2 exons

Exon	Start	End
ENSE00001476919	116942558	116944487
ENSE00001476924	116938207	116938567

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 85.69.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7629 / max 84.8040, expressed in 324 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90328	0.7073	293
90329	0.0557	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	85.69	gold quality
testis	UBERON:0000473	85.38	gold quality
right testis	UBERON:0004534	85.19	gold quality
mucosa of stomach	UBERON:0001199	83.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.83	gold quality
lower esophagus	UBERON:0013473	81.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	78.88	gold quality
urinary bladder	UBERON:0001255	73.76	gold quality
muscle layer of sigmoid colon	UBERON:0035805	72.04	gold quality
esophagus	UBERON:0001043	71.82	gold quality
fundus of stomach	UBERON:0001160	66.34	gold quality
prefrontal cortex	UBERON:0000451	63.97	gold quality
islet of Langerhans	UBERON:0000006	63.06	gold quality
esophagus mucosa	UBERON:0002469	63.06	gold quality
smooth muscle tissue	UBERON:0001135	62.10	gold quality
saliva-secreting gland	UBERON:0001044	61.92	gold quality
colon	UBERON:0001155	61.72	gold quality
minor salivary gland	UBERON:0001830	61.56	gold quality
left adrenal gland	UBERON:0001234	61.22	gold quality
skin of leg	UBERON:0001511	60.83	gold quality
right adrenal gland cortex	UBERON:0035827	60.57	gold quality
left adrenal gland cortex	UBERON:0035825	60.25	gold quality
superior frontal gyrus	UBERON:0002661	60.01	gold quality
right adrenal gland	UBERON:0001233	59.26	gold quality
adrenal gland	UBERON:0002369	59.15	gold quality
zone of skin	UBERON:0000014	59.06	gold quality
putamen	UBERON:0001874	58.93	gold quality
frontal cortex	UBERON:0001870	58.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.27
E-MTAB-6142	no	0.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting AARD, 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-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-493-5P	99.96	72.47	2382
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-1323	99.83	69.89	2471
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-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Aard	ENSMUSG00000068522
rattus_norvegicus	Aard	ENSRNOG00000004708

Paralogs (3): FAM167A (ENSG00000154319), FAM167B (ENSG00000183615), C20orf202 (ENSG00000215595)

Protein

Protein identifiers

Alanine- and arginine-rich domain-containing protein — Q4LEZ3 (reviewed: Q4LEZ3)

All UniProt accessions (1): Q4LEZ3

RefSeq proteins (1): NP_001020528* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR051771	FAM167_domain	Family

UniProt features (2 total): chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4LEZ3-F1	78.24	0.55

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): GOBP_RESPONSE_TO_TESTOSTERONE, GOBP_RESPONSE_TO_KETONE, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RESPONSE_TO_LIPID, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, LEE_BMP2_TARGETS_UP, MADAN_DPPA4_TARGETS, chr8q24, RAO_BOUND_BY_SALL4, GCNP_SHH_UP_LATE.V1_UP, WNT_UP.V1_DN, KAECH_DAY8_EFF_VS_DAY15_EFF_CD8_TCELL_DN, ZNF274_TARGET_GENES

GO Biological Process (1): response to testosterone (GO:0033574)

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
response to lipid	1
response to ketone	1
binding	1

Protein interactions and networks

STRING

214 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AARD	IQUB	Q8NA54	505
AARD	LRRC72	A6NJI9	448
AARD	CST9	Q5W186	431
AARD	SAXO4	Q7Z5V6	392
AARD	DLEC1	Q9Y238	381
AARD	SMG5	Q9UPR3	372
AARD	SMG7	Q92540	372
AARD	TMEM248	Q9NWD8	371
AARD	RPL12	P30050	371
AARD	SPMIP9	Q96LM6	368
AARD	UPF2	Q9HAU5	364
AARD	ARL10	Q8N8L6	360
AARD	CCDC116	Q8IYX3	354
AARD	SLC7A13	Q8TCU3	348
AARD	PLPP6	Q8IY26	336

IntAct

50 interactions, top by confidence:

A	B	Type	Score
AARD	KRT27	psi-mi:“MI:0915”(physical association)	0.630
KRT27	AARD	psi-mi:“MI:0915”(physical association)	0.630
KIAA0753	AARD	psi-mi:“MI:0915”(physical association)	0.560
STX2	AARD	psi-mi:“MI:0915”(physical association)	0.560
AARD	TSGA10	psi-mi:“MI:0915”(physical association)	0.560
STX5	AARD	psi-mi:“MI:0915”(physical association)	0.560
AARD	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
AARD	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.560
MAGEB4	AARD	psi-mi:“MI:0915”(physical association)	0.560
STX1A	AARD	psi-mi:“MI:0915”(physical association)	0.560
LMO4	AARD	psi-mi:“MI:0915”(physical association)	0.560
KRT24	AARD	psi-mi:“MI:0915”(physical association)	0.560
AARD	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
VPS37C	AARD	psi-mi:“MI:0915”(physical association)	0.560
AARD	CEP57	psi-mi:“MI:0915”(physical association)	0.560
AARD	CENPQ	psi-mi:“MI:0915”(physical association)	0.560
	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
AARD	KIAA0753	psi-mi:“MI:0915”(physical association)	0.000
AARD	STX2	psi-mi:“MI:0915”(physical association)	0.000
AARD	TSGA10	psi-mi:“MI:0915”(physical association)	0.000
AARD	STX5	psi-mi:“MI:0915”(physical association)	0.000
AARD	KRT27	psi-mi:“MI:0915”(physical association)	0.000
AARD	TFIP11	psi-mi:“MI:0915”(physical association)	0.000
AARD	GRIPAP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid), AARD (Two-hybrid)

ESM2 similar proteins: A1L168, A1L3T7, A6NGS2, A6QQF7, D4A8G3, O15049, P0C7N2, P0C7N4, P17257, P58660, Q08AY9, Q0V7M8, Q0VDN7, Q14BJ1, Q2NL23, Q3KP66, Q3LUD3, Q3UNU4, Q4LEZ3, Q566R4, Q571B6, Q5BJW5, Q5ND29, Q5RFZ7, Q5XIS1, Q6NSJ2, Q6P1G6, Q6Q0N2, Q7TN12, Q7TSI1, Q811W1, Q8BL43, Q8C7U1, Q8IV03, Q8K1S6, Q8K2P1, Q8N137, Q8N5H3, Q8TE77, Q8WWL2

Diamond homologs: Q4LEZ3, Q811W1, Q91ZF7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	0
Uncertain significance	28
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
145965	GRCh38/hg38 8q23.3-24.12(chr8:113418060-120975305)x1	Pathogenic
146552	GRCh38/hg38 8q23.3-24.12(chr8:112528342-120083041)x1	Pathogenic
150131	GRCh38/hg38 8q23.3-24.13(chr8:114560780-122594102)x1	Pathogenic
151754	GRCh38/hg38 8q22.1-24.3(chr8:97382873-145070385)x3	Pathogenic
152006	GRCh38/hg38 8q23.3-24.13(chr8:113933305-122621741)x1	Pathogenic
1527440	GRCh37/hg19 8q13.2-24.3(chr8:70382990-146295771)	Pathogenic
1527461	GRCh37/hg19 8q23.1-24.12(chr8:107032887-120742018)	Pathogenic
153413	GRCh38/hg38 8p23.3-q24.3(chr8:208048-145070385)x3	Pathogenic
154530	GRCh38/hg38 8q21.13-24.3(chr8:78614077-145054634)x3	Pathogenic
155592	GRCh38/hg38 8q21.2-24.3(chr8:85765999-145070385)x3	Pathogenic
1711167	GRCh37/hg19 8q13.2-24.3(chr8:68912432-146295771)x2	Pathogenic
1808681	GRCh37/hg19 8q21.12-24.11(chr8:79409349-119040631)x3	Pathogenic
1808708	GRCh37/hg19 8q23.3-24.22(chr8:112234557-133668379)x1	Pathogenic
253639	GRCh37/hg19 8q24.11(chr8:117714768-119072307)x1	Pathogenic
2579176	GRCh38/hg38 8q23.3-24.23(chr8:115586904-135607135)x3	Pathogenic
3245509	NC_000008.10:g.(?116426251)(120844804_?)del	Pathogenic
3245563	NC_000008.10:g.(?116426251)(119965024_?)del	Pathogenic
395449	GRCh37/hg19 8q22.1-24.3(chr8:98432250-146222672)x4	Pathogenic
441594	GRCh37/hg19 8q21.2-24.3(chr8:86841228-142689874)x3	Pathogenic
441733	GRCh37/hg19 8q23.2-24.12(chr8:111137305-119897611)x1	Pathogenic
441804	GRCh37/hg19 8q21.3-24.3(chr8:93047482-141355635)x3	Pathogenic
442201	GRCh37/hg19 8p23.3-q24.3(chr8:158049-146295771)x3	Pathogenic
442692	GRCh37/hg19 8q23.3-24.3(chr8:114853126-146295771)x3	Pathogenic
443924	GRCh37/hg19 8q21.2-24.3(chr8:86841154-146295771)x3	Pathogenic
563549	GRCh37/hg19 8q23.1-24.13(chr8:110250943-123515785)x1	Pathogenic
57045	GRCh38/hg38 8q23.3-24.3(chr8:113580402-145054634)x3	Pathogenic
60403	GRCh38/hg38 8q23.3-24.21(chr8:113288454-126716087)x1	Pathogenic
687493	GRCh37/hg19 8p12-q24.3(chr8:31936551-146295771)x3	Pathogenic
815154	GRCh37/hg19 8q23.2-24.13(chr8:111514791-123192373)x1	Pathogenic
979849	GRCh37/hg19 8q23.1-24.13(chr8:108421573-123429638)x3	Pathogenic

SpliceAI

180 predictions. Top by Δscore:

Variant	Effect	Δscore
8:116938484:G:GT	donor_gain	1.0000
8:116938564:GCTG:G	donor_gain	0.9900
8:116942550:A:AG	acceptor_gain	0.9900
8:116942553:TTTA:T	acceptor_loss	0.9900
8:116942554:TTA:T	acceptor_loss	0.9900
8:116942555:TA:T	acceptor_loss	0.9900
8:116942556:A:AG	acceptor_gain	0.9900
8:116942556:AGGT:A	acceptor_gain	0.9900
8:116942557:G:GA	acceptor_gain	0.9900
8:116942557:GGTG:G	acceptor_gain	0.9900
8:116938530:GCGT:G	donor_gain	0.9800
8:116938568:G:GG	donor_gain	0.9800
8:116938725:G:GT	donor_gain	0.9800
8:116938725:G:T	donor_gain	0.9800
8:116942549:A:AG	acceptor_gain	0.9800
8:116942557:GGT:G	acceptor_gain	0.9800
8:116938565:CTGGT:C	donor_loss	0.9700
8:116938566:TGG:T	donor_loss	0.9700
8:116938568:GTGAG:G	donor_loss	0.9700
8:116938569:T:A	donor_loss	0.9700
8:116938570:GAGA:G	donor_loss	0.9700
8:116942551:C:G	acceptor_gain	0.9700
8:116942556:AG:A	acceptor_gain	0.9700
8:116942556:AGGTG:A	acceptor_gain	0.9700
8:116942557:GG:G	acceptor_gain	0.9700
8:116942557:GGTGG:G	acceptor_gain	0.9700
8:116938529:GGCGT:G	donor_gain	0.9600
8:116938552:GC:G	donor_gain	0.9500
8:116938446:A:AG	donor_gain	0.9400
8:116938447:G:GG	donor_gain	0.9400

AlphaMissense

1001 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:116942566:G:A	M111I	0.864
8:116942566:G:C	M111I	0.864
8:116942566:G:T	M111I	0.864
8:116942570:T:C	F113L	0.847
8:116942572:C:A	F113L	0.847
8:116942572:C:G	F113L	0.847
8:116942628:T:C	L132S	0.825
8:116942565:T:C	M111T	0.821
8:116942632:A:C	K133N	0.816
8:116942632:A:T	K133N	0.816
8:116942607:T:C	L125P	0.800
8:116942586:T:C	L118P	0.786
8:116938442:T:C	F67L	0.778
8:116938444:C:A	F67L	0.778
8:116938444:C:G	F67L	0.778
8:116942610:A:T	N126I	0.777
8:116942631:A:T	K133I	0.742
8:116942598:T:C	L122S	0.725
8:116942578:C:A	N115K	0.720
8:116942578:C:G	N115K	0.720
8:116942575:A:C	Q114H	0.718
8:116942575:A:T	Q114H	0.718
8:116942617:A:C	K128N	0.712
8:116942617:A:T	K128N	0.712
8:116942616:A:T	K128I	0.701
8:116938554:T:C	L104P	0.682
8:116942577:A:T	N115I	0.681
8:116942588:G:C	A119P	0.675
8:116942589:C:A	A119D	0.671
8:116942595:C:T	T121I	0.663

dbSNP variants (sampled 300 via entrez): RS1000126988 (8:116939771 C>A), RS1001196148 (8:116936394 C>T), RS1001199565 (8:116939710 C>A,T), RS1001273251 (8:116939467 A>G), RS1001946358 (8:116944794 T>C), RS1001978966 (8:116944310 A>T), RS1002774540 (8:116939818 T>C), RS1003215301 (8:116939493 A>G), RS1004042697 (8:116937738 C>A), RS1004205918 (8:116944088 C>A), RS1004360918 (8:116943756 C>A,T), RS1004379138 (8:116938021 T>A), RS1004402047 (8:116937636 G>A,C,T), RS1004744555 (8:116938954 C>T), RS1004944970 (8:116943968 A>T)

Disease associations

OMIM: gene MIM:621042 | disease phenotypes: MIM:133700, MIM:190350

GenCC curated gene-disease

Mondo (4): hereditary multiple osteochondromas (MONDO:0005508), neurodevelopmental disorder (MONDO:0700092), trichorhinophalangeal syndrome type I (MONDO:0008596), intellectual disability (MONDO:0001071)

Orphanet (3): Multiple osteochondromas (Orphanet:321), Trichorhinophalangeal syndrome type 1 (Orphanet:77258), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006957_3	Severe aortic features in Marfan syndrome	5.000000e-06

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D005097	Exostoses, Multiple Hereditary	C04.557.450.565.575.610.615.325; C04.700.330; C05.116.099.708.670.615.325; C05.116.540.310.500; C16.320.700.330
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C536820	Trichorhinophalangeal Syndrome, Type I (supp.)

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 A	decreases expression	1
ferrous chloride	decreases expression	1
(+)-JQ1 compound	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Triclosan	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
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